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1
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Liu YL, Chen XW, Tian SQ, Tan XH, Peng B. Edwardsiella tarda Attenuates Virulence upon Oxytetracycline Resistance. J Proteome Res 2024; 23:2576-2586. [PMID: 38860290 DOI: 10.1021/acs.jproteome.4c00303] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 06/12/2024]
Abstract
The relationship between antibiotic resistance and bacterial virulence has not yet been fully explored. Here, we use Edwardsiella tarda as the research model to investigate the proteomic change upon oxytetracycline resistance (LTB4-ROTC). Compared to oxytetracycline-sensitive E. tarda (LTB4-S), LTB4-ROTC has 234 differentially expressed proteins, of which the abundance of 84 proteins is downregulated and 15 proteins are enriched to the Type III secretion system, Type VI secretion system, and flagellum pathways. Functional analysis confirms virulent phenotypes, including autoaggregation, biofilm formation, hemolysis, swimming, and swarming, are impaired in LTB4-ROTC. Furthermore, the in vivo bacterial challenge in both tilapia and zebrafish infection models suggests that the virulence of LTB4-ROTC is attenuated. Analysis of immune gene expression shows that LTB4-ROTC induces a stronger immune response in the spleen but a weaker response in the head kidney than that induced by LTB4-S, suggesting it's a potential vaccine candidate. Zebrafish and tilapia were challenged with a sublethal dose of LTB4-ROTC as a live vaccine followed by LTB4-S challenge. The relative percentage of survival of zebrafish is 60% and that of tilapia is 75% after vaccination. Thus, our study suggests that bacteria that acquire antibiotic resistance may attenuate virulence, which can be explored as a potential live vaccine to tackle bacterial infection in aquaculture.
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Affiliation(s)
- Ying-Li Liu
- State Key Laboratory of Biocontrol, Guangdong Key Laboratory of Pharmaceutical Functional Genes, School of Life Sciences, Southern Marine Science and Engineering Guangdong Laboratory (Zhuhai), Sun Yat-sen University, Guangzhou 510275, People's Republic of China
| | - Xuan-Wei Chen
- State Key Laboratory of Biocontrol, Guangdong Key Laboratory of Pharmaceutical Functional Genes, School of Life Sciences, Southern Marine Science and Engineering Guangdong Laboratory (Zhuhai), Sun Yat-sen University, Guangzhou 510275, People's Republic of China
| | - Si-Qi Tian
- State Key Laboratory of Biocontrol, Guangdong Key Laboratory of Pharmaceutical Functional Genes, School of Life Sciences, Southern Marine Science and Engineering Guangdong Laboratory (Zhuhai), Sun Yat-sen University, Guangzhou 510275, People's Republic of China
| | - Xiao-Hua Tan
- State Key Laboratory of Biocontrol, Guangdong Key Laboratory of Pharmaceutical Functional Genes, School of Life Sciences, Southern Marine Science and Engineering Guangdong Laboratory (Zhuhai), Sun Yat-sen University, Guangzhou 510275, People's Republic of China
| | - Bo Peng
- State Key Laboratory of Biocontrol, Guangdong Key Laboratory of Pharmaceutical Functional Genes, School of Life Sciences, Southern Marine Science and Engineering Guangdong Laboratory (Zhuhai), Sun Yat-sen University, Guangzhou 510275, People's Republic of China
- Laboratory for Marine Biology and Biotechnology, Qingdao Marine Science and Technology Center, Qingdao 266071, China
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2
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Matz H, Taylor RS, Redmond AK, Hill TM, Ruiz Daniels R, Beltran M, Henderson NC, Macqueen DJ, Dooley H. Organized B cell sites in cartilaginous fishes reveal the evolutionary foundation of germinal centers. Cell Rep 2023; 42:112664. [PMID: 37342909 PMCID: PMC10529500 DOI: 10.1016/j.celrep.2023.112664] [Citation(s) in RCA: 14] [Impact Index Per Article: 7.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/19/2022] [Revised: 02/28/2023] [Accepted: 06/04/2023] [Indexed: 06/23/2023] Open
Abstract
The absence of germinal centers (GCs) in cartilaginous fishes lies at odds with data showing that nurse sharks can produce robust antigen-specific responses and affinity mature their B cell repertoires. To investigate this apparent incongruity, we performed RNA sequencing on single nuclei, allowing us to characterize the cell types present in the nurse shark spleen, and RNAscope to provide in situ cellular resolution of key marker gene expression following immunization with R-phycoerythrin (PE). We tracked PE to the splenic follicles where it co-localizes with CXCR5high centrocyte-like B cells and a population of putative T follicular helper (Tfh) cells, surrounded by a peripheral ring of Ki67+ AID+ CXCR4+ centroblast-like B cells. Further, we reveal selection of mutations in B cell clones dissected from these follicles. We propose that the B cell sites identified here represent the evolutionary foundation of GCs, dating back to the jawed vertebrate ancestor.
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Affiliation(s)
- Hanover Matz
- Department of Microbiology and Immunology, University of Maryland School of Medicine, Institute of Marine and Environmental Technology, Baltimore, MD, USA
| | - Richard S Taylor
- The Roslin Institute and Royal (Dick) School of Veterinary Studies, University of Edinburgh, Edinburgh, UK
| | - Anthony K Redmond
- Smurfit Institute of Genetics, Trinity College Dublin, Dublin, Ireland
| | - Thomas M Hill
- Department of Microbiology and Immunology, University of Maryland School of Medicine, Institute of Marine and Environmental Technology, Baltimore, MD, USA
| | - Rose Ruiz Daniels
- The Roslin Institute and Royal (Dick) School of Veterinary Studies, University of Edinburgh, Edinburgh, UK
| | - Mariana Beltran
- Centre for Inflammation Research, The Queen's Medical Research Institute, Edinburgh BioQuarter, University of Edinburgh, Edinburgh, UK
| | - Neil C Henderson
- Centre for Inflammation Research, The Queen's Medical Research Institute, Edinburgh BioQuarter, University of Edinburgh, Edinburgh, UK; MRC Human Genetics Unit, Institute of Genetics and Molecular Medicine, University of Edinburgh, Edinburgh, UK
| | - Daniel J Macqueen
- The Roslin Institute and Royal (Dick) School of Veterinary Studies, University of Edinburgh, Edinburgh, UK
| | - Helen Dooley
- Department of Microbiology and Immunology, University of Maryland School of Medicine, Institute of Marine and Environmental Technology, Baltimore, MD, USA.
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3
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Stosik M, Tokarz-Deptuła B, Deptuła W. Immunity of the intestinal mucosa in teleost fish. FISH & SHELLFISH IMMUNOLOGY 2023; 133:108572. [PMID: 36717066 DOI: 10.1016/j.fsi.2023.108572] [Citation(s) in RCA: 14] [Impact Index Per Article: 7.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Received: 05/25/2022] [Revised: 01/26/2023] [Accepted: 01/26/2023] [Indexed: 06/18/2023]
Abstract
The paper presents the problem of intestinal mucosa immunity in teleost fish. The immunity of the intestinal mucosa in teleost fish depends on the elements and mechanisms with different organizational/structural and functional properties than in mammals. The organization of the elements of intestinal mucosal immunitya in these animals is associated with the presence of immune cells that fulfil the functions assigned to the induction and effector sites of mucosal immunity in mammals; they are located at various histological sites of the mucosa - in the lamina propria (LP) and in the surface epithelium. The presence of mucosa-associated lymphoid tissue (MALT) has not been demonstrated in teleost fish, and the terminology used in relation to the structure and function of the mucosa immunity components in teleost fish is inadequate. In this article, we review the knowledge of intestinal mucosal immunity in teleost fish, with great potential for knowledge and practical applications especially in the field of epidemiological safety. We discuss the organization and functional properties of the elements that determine this immunity, according to current data and taking into account the tissue definition and terminology adopted by the Society for Mucosal Immunology General Assembly (13th ICMI in Tokyo, 2007).
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Affiliation(s)
- Michał Stosik
- Institute of Biological Sciences, University of Zielona Góra, Poland
| | | | - Wiesław Deptuła
- Institute of Veterinary Medicine, Faculty of Biological and Veterinary Sciences, Nicolaus Copernicus University in Toruń, Poland
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4
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Etayo A, Lie KK, Bjelland RM, Hordvik I, Øvergård AC, Sæle Ø. The thymus and T-cell ontogeny in ballan wrasse ( Labrus bergylta) is nutritionally modelled. Front Immunol 2023; 14:1166785. [PMID: 37197651 PMCID: PMC10183603 DOI: 10.3389/fimmu.2023.1166785] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/10/2023] [Accepted: 04/20/2023] [Indexed: 05/19/2023] Open
Abstract
Marine fish larvae often experience high mortality unrelated to predation during early life stages, and farmed ballan wrasse (Labrus bergylta) is no exception. Knowing when the adaptive immune system is developed and fully functional, and how nutrition may modulate these processes is therefore of importance to establish effective prophylactic measures and will also extend the relatively limited knowledge on the immune system in lower vertebrates. The thymus anlage of ballan wrasse was found to be histologically visible for the first time at larval stage 3 (20-30 days post hatch, dph) and becomes lymphoid at stage 5 (50-60 dph) correlating with an increase of T-cell marker transcripts. At this stage, a clear zonation into a RAG1+ cortex and a RAG1- CD3ϵ+ medulla was distinguished, indicating that T-cell maturation processes in ballan wrasse are similar to other teleosts. The higher abundance of CD4-1+ compared to CD8β+ cells in the thymus together with the apparent lack of CD8β+ cells in gill, gut, and pharynx, where CD4-1+ cells were identified, indicates that helper T-cells have a more prominent role during larval development compared to cytotoxic T-cells. As ballan wrasse lacks a stomach but has an exceptionally high IgM expression in the hindgut, we hypothesize that helper T-cells are crucial for activation and recruitment of IgM+ B-cells and possibly other leukocytes to the gut during early development. Nutritional factors such as DHA/EPA, Zn and Se may lead to an earlier expression of certain T-cell markers as well as a larger size of the thymus, indicating an earlier onset of adaptive immunity. Including live feeds that supplies the larva with higher amounts of these nutrients can therefore be beneficial for ballan wrasse farming.
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Affiliation(s)
- Angela Etayo
- Feed and Nutrition group, Institute of Marine Research, Bergen, Norway
- Fish Health Group, Department of Biological Sciences, University of Bergen, Bergen, Norway
- *Correspondence: Angela Etayo,
| | - Kai K. Lie
- Feed and Nutrition group, Institute of Marine Research, Bergen, Norway
| | - Reidun M. Bjelland
- Institute of Marine Research, Austevoll Research Station, Storebø, Norway
| | - Ivar Hordvik
- Fish Health Group, Department of Biological Sciences, University of Bergen, Bergen, Norway
| | - Aina-Cathrine Øvergård
- Fish Health Group, Department of Biological Sciences, University of Bergen, Bergen, Norway
| | - Øystein Sæle
- Feed and Nutrition group, Institute of Marine Research, Bergen, Norway
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5
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Zapata AG. Lympho-Hematopoietic Microenvironments and Fish Immune System. BIOLOGY 2022; 11:747. [PMID: 35625475 PMCID: PMC9138301 DOI: 10.3390/biology11050747] [Citation(s) in RCA: 10] [Impact Index Per Article: 3.3] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 04/09/2022] [Revised: 05/10/2022] [Accepted: 05/11/2022] [Indexed: 12/20/2022]
Abstract
In the last 50 years information on the fish immune system has increased importantly, particularly that on species of marked commercial interest (i.e., salmonids, cods, catfish, sea breams), that occupy a key position in the vertebrate phylogenetical tree (i.e., Agnatha, Chondrichtyes, lungfish) or represent consolidated experimental models, such as zebrafish or medaka. However, most obtained information was based on genetic sequence analysis with little or no information on the cellular basis of the immune responses. Although jawed fish contain a thymus and lympho-hematopoietic organs equivalents to mammalian bone marrow, few studies have accounted for the presumptive relationships between the organization of these cell microenvironments and the known immune capabilities of the fish immune system. In the current review, we analyze this topic providing information on: (1) The origins of T and B lymphopoiesis in Agnatha and jawed fish; (2) the remarkable organization of the thymus of teleost fish; (3) the occurrence of numerous, apparently unrelated organs housing lympho-hematopoietic progenitors and, presumably, B lymphopoiesis; (4) the existence of fish immunological memory in the absence of germinal centers.
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Affiliation(s)
- Agustín G. Zapata
- Department of Cell Biology, Faculty of Biology, Complutense University of Madrid, 28040 Madrid, Spain; ; Tel.: +34-913-944-979
- Health Research Institute, Hospital 12 de Octubre (imas12), 28041 Madrid, Spain
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6
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Dalum AS, Kraus A, Khan S, Davydova E, Rigaudeau D, Bjørgen H, López-Porras A, Griffiths G, Wiegertjes GF, Koppang EO, Salinas I, Boudinot P, Rességuier J. High-Resolution, 3D Imaging of the Zebrafish Gill-Associated Lymphoid Tissue (GIALT) Reveals a Novel Lymphoid Structure, the Amphibranchial Lymphoid Tissue. Front Immunol 2021; 12:769901. [PMID: 34880866 PMCID: PMC8647647 DOI: 10.3389/fimmu.2021.769901] [Citation(s) in RCA: 24] [Impact Index Per Article: 6.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/02/2021] [Accepted: 10/25/2021] [Indexed: 12/24/2022] Open
Abstract
The zebrafish is extensively used as an animal model for human and fish diseases. However, our understanding of the structural organization of its immune system remains incomplete, especially the mucosa-associated lymphoid tissues (MALTs). Teleost MALTs are commonly perceived as diffuse and scattered populations of immune cells throughout the mucosa. Yet, structured MALTs have been recently discovered in Atlantic salmon (Salmo salar L.), including the interbranchial lymphoid tissue (ILT) in the gills. The existence of the ILT was only recently identified in zebrafish and other fish species, highlighting the need for in-depth characterizations of the gill-associated lymphoid tissue (GIALT) in teleosts. Here, using 3-D high-resolution microscopy, we analyze the GIALT of adult zebrafish with an immuno-histology approach that reveals the organization of lymphoid tissues via the labeling of T/NK cells with an antibody directed to a highly conserved epitope on the kinase ZAP70. We show that the GIALT in zebrafish is distributed over at least five distinct sub-regions, an organization found in all pairs of gill arches. The GIALT is diffuse in the pharyngeal part of the gill arch, the interbranchial septum and the filaments/lamellae, and structured in two sub-regions: the ILT, and a newly discovered lymphoid structure located along each side of the gill arch, which we named the Amphibranchial Lymphoid Tissue (ALT). Based on RAG2 expression, neither the ILT nor the ALT constitute additional thymi. The ALT shares several features with the ILT such as presence of abundant lymphoid cells and myeloid cells embedded in a network of reticulated epithelial cells. Further, the ILT and the ALT are also a site for T/NK cell proliferation. Both ILT and ALT show structural changes after infection with Spring Viraemia of Carp Virus (SVCV). Together, these data suggest that ALT and ILT play an active role in immune responses. Comparative studies show that whereas the ILT seems absent in most neoteleosts ("Percomorphs"), the ALT is widely present in cyprinids, salmonids and neoteleosts, suggesting that it constitutes a conserved tissue involved in the protection of teleosts via the gills.
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Affiliation(s)
- Alf S. Dalum
- Nofima, Norwegian Institute of Food, Fisheries and Aquaculture Research, Ås, Norway
| | - Aurora Kraus
- Center for Evolutionary and Theoretical Immunology (CETI), Department of Biology, University of New Mexico, Albuquerque, NM, United States
| | - Shanawaz Khan
- Department of Biosciences, FYSCELL, University of Oslo, Oslo, Norway
| | - Erna Davydova
- Department of Biosciences, BMB, University of Oslo, Oslo, Norway
| | | | - Håvard Bjørgen
- Section of Anatomy, Faculty of Veterinary Medicine, Norwegian University of Life Sciences, Ås, Norway
| | | | - Gareth Griffiths
- Department of Biosciences, FYSCELL, University of Oslo, Oslo, Norway
| | - Geert F. Wiegertjes
- Aquaculture and Fisheries Group, Department of Animal Sciences, Wageningen University & Research, Wageningen, Netherlands
| | - Erling O. Koppang
- Section of Anatomy, Faculty of Veterinary Medicine, Norwegian University of Life Sciences, Ås, Norway
| | - Irene Salinas
- Center for Evolutionary and Theoretical Immunology (CETI), Department of Biology, University of New Mexico, Albuquerque, NM, United States
| | - Pierre Boudinot
- INRAE, UVSQ, VIM, Université Paris-Saclay, Jouy-en-Josas, France
| | - Julien Rességuier
- Department of Biosciences, FYSCELL, University of Oslo, Oslo, Norway
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7
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Holzer AS, Piazzon MC, Barrett D, Bartholomew JL, Sitjà-Bobadilla A. To React or Not to React: The Dilemma of Fish Immune Systems Facing Myxozoan Infections. Front Immunol 2021; 12:734238. [PMID: 34603313 PMCID: PMC8481699 DOI: 10.3389/fimmu.2021.734238] [Citation(s) in RCA: 15] [Impact Index Per Article: 3.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/30/2021] [Accepted: 09/01/2021] [Indexed: 11/13/2022] Open
Abstract
Myxozoans are microscopic, metazoan, obligate parasites, belonging to the phylum Cnidaria. In contrast to the free-living lifestyle of most members of this taxon, myxozoans have complex life cycles alternating between vertebrate and invertebrate hosts. Vertebrate hosts are primarily fish, although they are also reported from amphibians, reptiles, trematodes, mollusks, birds and mammals. Invertebrate hosts include annelids and bryozoans. Most myxozoans are not overtly pathogenic to fish hosts, but some are responsible for severe economic losses in fisheries and aquaculture. In both scenarios, the interaction between the parasite and the host immune system is key to explain such different outcomes of this relationship. Innate immune responses contribute to the resistance of certain fish strains and species, and the absence or low levels of some innate and regulatory factors explain the high pathogenicity of some infections. In many cases, immune evasion explains the absence of a host response and allows the parasite to proliferate covertly during the first stages of the infection. In some infections, the lack of an appropriate regulatory response results in an excessive inflammatory response, causing immunopathological consequences that are worse than inflicted by the parasite itself. This review will update the available information about the immune responses against Myxozoa, with special focus on T and B lymphocyte and immunoglobulin responses, how these immune effectors are modulated by different biotic and abiotic factors, and on the mechanisms of immune evasion targeting specific immune effectors. The current and future design of control strategies for myxozoan diseases is based on understanding this myxozoan-fish interaction, and immune-based strategies such as improvement of innate and specific factors through diets and additives, host genetic selection, passive immunization and vaccination, are starting to be considered.
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Affiliation(s)
- Astrid S Holzer
- Institute of Parasitology, Biology Centre of the Czech Academy of Sciences, České Budějovice, Czechia
| | - M Carla Piazzon
- Fish Pathology Group, Institute of Aquaculture Torre de la Sal - Consejo Superior de Investigaciones Científicas (IATS-CSIC), Castellón, Spain
| | - Damien Barrett
- Department of Microbiology, Oregon State University, Corvallis, OR, United States
| | - Jerri L Bartholomew
- Department of Microbiology, Oregon State University, Corvallis, OR, United States
| | - Ariadna Sitjà-Bobadilla
- Fish Pathology Group, Institute of Aquaculture Torre de la Sal - Consejo Superior de Investigaciones Científicas (IATS-CSIC), Castellón, Spain
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8
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Kogame T, Kabashima K, Egawa G. Putative Immunological Functions of Inducible Skin-Associated Lymphoid Tissue in the Context of Mucosa-Associated Lymphoid Tissue. Front Immunol 2021; 12:733484. [PMID: 34512668 PMCID: PMC8426509 DOI: 10.3389/fimmu.2021.733484] [Citation(s) in RCA: 4] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/30/2021] [Accepted: 08/05/2021] [Indexed: 12/12/2022] Open
Abstract
Acquired immunity is orchestrated in various lymphoid organs, including bone marrow, thymus, spleen, and lymph nodes in humans. However, mucosa-associated lymphoid tissue (MALT) is evolutionally known to be emerged in the oldest vertebrates as an immunological tissue for acquired immunity, much earlier than the advent of lymph nodes which appeared in endotherms. Furthermore, the lymphocytes which developed in MALT are known to circulate within the limited anatomical areas. Thus, MALT is comprehended as not the structure but the immune network dedicated to local immunity. As for the skin, skin-associated lymphoid tissue (SALT) was previously postulated; however, its existence has not been proven. Our group recently showed that aggregations of dendritic cells, M2 macrophages, and high endothelial venules (HEVs) are essential components to activate effector T cells in the murine contact hypersensitivity model and termed it as inducible SALT (iSALT) since it was a transient entity that serves for acquired immunity of the skin. Furthermore, in various human skin diseases, we reported that the ectopic formation of lymphoid follicles that immunohistochemically analogous to MALT and regarded them as human counterparts of iSALT. These data raised the possibility that SALT can exist as an inducible form, namely iSALT, which shares the biological significance of MALT. In this article, we revisit the evolution of immunological organs and the related components among vertebrates to discuss the conserved functions of MALT. Furthermore, we also discuss the putative characteristics and functions of iSALT in the context of the MALT concept.
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Affiliation(s)
- Toshiaki Kogame
- Department of Dermatology, Kyoto University Graduate School of Medicine, Kyoto, Japan
| | - Kenji Kabashima
- Department of Dermatology, Kyoto University Graduate School of Medicine, Kyoto, Japan
| | - Gyohei Egawa
- Department of Dermatology, Kyoto University Graduate School of Medicine, Kyoto, Japan
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9
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Bjørgen H, Koppang EO. Anatomy of teleost fish immune structures and organs. Immunogenetics 2021; 73:53-63. [PMID: 33426583 PMCID: PMC7862538 DOI: 10.1007/s00251-020-01196-0] [Citation(s) in RCA: 84] [Impact Index Per Article: 21.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/01/2020] [Accepted: 11/23/2020] [Indexed: 12/13/2022]
Abstract
The function of a tissue is determined by its construction and cellular composition. The action of different genes can thus only be understood properly when seen in the context of the environment in which they are expressed and function. We now experience a renaissance in morphological research in fish, not only because, surprisingly enough, large structures have remained un-described until recently, but also because improved methods for studying morphological characteristics in combination with expression analysis are at hand. In this review, we address anatomical features of teleost immune tissues. There are approximately 30,000 known teleost fish species and only a minor portion of them have been studied. We aim our review at the Atlantic salmon (Salmo salar) and other salmonids, but when applicable, we also present information from other species. Our focus is the anatomy of the kidney, thymus, spleen, the interbranchial lymphoid tissue (ILT), the newly discovered salmonid cloacal bursa and the naso-pharynx associated lymphoid tissue (NALT).
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Affiliation(s)
- Håvard Bjørgen
- Section of Anatomy, The Faculty of Veterinary Medicine, Norwegian University of Life Sciences, Ullevålsveien 72, Oslo, Norway
| | - Erling Olaf Koppang
- Section of Anatomy, The Faculty of Veterinary Medicine, Norwegian University of Life Sciences, Ullevålsveien 72, Oslo, Norway.
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10
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Soleto I, Morel E, Muñoz-Atienza E, Díaz-Rosales P, Tafalla C. Aeromonas salmonicida activates rainbow trout IgM + B cells signalling through Toll like receptors. Sci Rep 2020; 10:16810. [PMID: 33033353 PMCID: PMC7545209 DOI: 10.1038/s41598-020-73999-w] [Citation(s) in RCA: 11] [Impact Index Per Article: 2.2] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/16/2019] [Accepted: 09/16/2020] [Indexed: 12/18/2022] Open
Abstract
As B cells are singularly equipped with a B cell receptor (BCR) and a range of innate receptors, they are able to integrate both antigen-specific and innate signals, with the latter being essential to reach an adequate level of activation. Whether teleost B cells sense pathogens through innate mechanisms has not yet been explored, despite the fact that fish B cells display a wider array of innate receptors than many mammalian B cell subsets. Hence, in the current study, we have investigated the effects of inactivated Aeromonas salmonicida, a Gram negative rainbow trout pathogen, on trout splenic IgM+ B cells in vitro in the presence or absence of different inhibitors of Toll-like receptor (TLR) signalling, to establish to what degree innate signals are contributing to the activation of B cells in teleosts. Our results demonstrate that most of the effects that A. salmonicida exerts on trout IgM+ B cells are significantly blocked in the presence of inhibitors of MyD88 and TRIF, important nodes in TLR signal pathways. Thus, the data presented demonstrates that, also in teleost, TLR signalling is essential for the activation of IgM+ B cells. These results will be useful for the future optimization of novel vaccines and adjuvants.
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Affiliation(s)
- Irene Soleto
- Fish Immunology and Pathology Laboratory, Animal Health Research Center (CISA-INIA), Valdeolmos, Madrid, Spain
| | - Esther Morel
- Fish Immunology and Pathology Laboratory, Animal Health Research Center (CISA-INIA), Valdeolmos, Madrid, Spain
| | - Estefanía Muñoz-Atienza
- Fish Immunology and Pathology Laboratory, Animal Health Research Center (CISA-INIA), Valdeolmos, Madrid, Spain
| | - Patricia Díaz-Rosales
- Fish Immunology and Pathology Laboratory, Animal Health Research Center (CISA-INIA), Valdeolmos, Madrid, Spain
| | - Carolina Tafalla
- Fish Immunology and Pathology Laboratory, Animal Health Research Center (CISA-INIA), Valdeolmos, Madrid, Spain.
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11
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Heubel BP, Bredesen CA, Schilling TF, Le Pabic P. Endochondral growth zone pattern and activity in the zebrafish pharyngeal skeleton. Dev Dyn 2020; 250:74-87. [PMID: 32852849 DOI: 10.1002/dvdy.241] [Citation(s) in RCA: 9] [Impact Index Per Article: 1.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/15/2020] [Revised: 08/19/2020] [Accepted: 08/22/2020] [Indexed: 12/13/2022] Open
Abstract
BACKGROUND Endochondral ossification is a major bone forming mechanism in vertebrates, defects in which can result in skeletal dysplasia or craniofacial anomalies in humans. The zebrafish holds great potential to advance our understanding of endochondral growth zone development and genetics, yet several important aspects of its biology remain unexplored. Here we provide a comprehensive description of endochondral growth zones in the pharyngeal skeleton, including their developmental progression, cellular activity, and adult fates. RESULTS Postembryonic growth of the pharyngeal skeleton is supported by endochondral growth zones located either at skeletal epiphyses or synchondroses. Col2a1a and col10a1a in situ hybridization and anti-PCNA immunostaining identify resting-, hypertrophic- and proliferative zones, respectively, in pharyngeal synchondroses. Cellular hypertrophy and matrix deposition contribute little, if at all, to axial growth in most skeletal elements. Zebrafish endochondral growth zones develop during metamorphosis and arrest in adults. CONCLUSIONS Two endochondral growth zone configurations in the zebrafish pharyngeal skeleton produce either unidirectional (epiphyses) or bidirectional (synchondroses) growth. Cell proliferation drives endochondral growth and its modulation, in contrast to mammalian long bones in which bone length depends more on cell enlargement during hypertrophy and intramembranous ossification is the default mechanism of bone growth in zebrafish adults.
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Affiliation(s)
- Brian P Heubel
- Department of Biological Sciences, University of Delaware, Newark, Delaware, USA
| | - Carson A Bredesen
- Department of Biology and Marine Biology, University of North Carolina Wilmington, Wilmington, North Carolina, USA
| | - Thomas F Schilling
- Department of Developmental and Cell Biology, University of California Irvine, Irvine, California, USA
| | - Pierre Le Pabic
- Department of Biology and Marine Biology, University of North Carolina Wilmington, Wilmington, North Carolina, USA
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12
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Heimroth RD, Casadei E, Salinas I. Molecular Drivers of Lymphocyte Organization in Vertebrate Mucosal Surfaces: Revisiting the TNF Superfamily Hypothesis. JOURNAL OF IMMUNOLOGY (BALTIMORE, MD. : 1950) 2020; 204:2697-2711. [PMID: 32238457 PMCID: PMC7872792 DOI: 10.4049/jimmunol.1901059] [Citation(s) in RCA: 6] [Impact Index Per Article: 1.2] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Subscribe] [Scholar Register] [Received: 08/30/2019] [Accepted: 02/26/2020] [Indexed: 12/19/2022]
Abstract
The adaptive immune system of all jawed vertebrates relies on the presence of B and T cell lymphocytes that aggregate in specific body sites to form primary and secondary lymphoid structures. Secondary lymphoid organs include organized MALT (O-MALT) such as the tonsils and Peyer patches. O-MALT became progressively organized during vertebrate evolution, and the TNF superfamily of genes has been identified as essential for the formation and maintenance of O-MALT and other secondary and tertiary lymphoid structures in mammals. Yet, the molecular drivers of O-MALT structures found in ectotherms and birds remain essentially unknown. In this study, we provide evidence that TNFSFs, such as lymphotoxins, are likely not a universal mechanism to maintain O-MALT structures in adulthood of teleost fish, sarcopterygian fish, or birds. Although a role for TNFSF2 (TNF-α) cannot be ruled out, transcriptomics suggest that maintenance of O-MALT in nonmammalian vertebrates relies on expression of diverse genes with shared biological functions in neuronal signaling. Importantly, we identify that expression of many genes with olfactory function is a unique feature of mammalian Peyer patches but not the O-MALT of birds or ectotherms. These results provide a new view of O-MALT evolution in vertebrates and indicate that different genes with shared biological functions may have driven the formation of these lymphoid structures by a process of convergent evolution.
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Affiliation(s)
- Ryan D Heimroth
- Center for Evolutionary and Theoretical Immunology, University of New Mexico, Albuquerque, NM 87131; and
- Department of Biology, University of New Mexico, Albuquerque, NM 87131
| | - Elisa Casadei
- Center for Evolutionary and Theoretical Immunology, University of New Mexico, Albuquerque, NM 87131; and
- Department of Biology, University of New Mexico, Albuquerque, NM 87131
| | - Irene Salinas
- Center for Evolutionary and Theoretical Immunology, University of New Mexico, Albuquerque, NM 87131; and
- Department of Biology, University of New Mexico, Albuquerque, NM 87131
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13
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Wentzel AS, Janssen JJE, de Boer VCJ, van Veen WG, Forlenza M, Wiegertjes GF. Fish Macrophages Show Distinct Metabolic Signatures Upon Polarization. Front Immunol 2020; 11:152. [PMID: 32158446 PMCID: PMC7052297 DOI: 10.3389/fimmu.2020.00152] [Citation(s) in RCA: 35] [Impact Index Per Article: 7.0] [Reference Citation Analysis] [Abstract] [Key Words] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/02/2019] [Accepted: 01/21/2020] [Indexed: 01/09/2023] Open
Abstract
Macrophages play important roles in conditions ranging from host immune defense to tissue regeneration and polarize their functional phenotype accordingly. Next to differences in the use of L-arginine and the production of different cytokines, inflammatory M1 macrophages and anti-inflammatory M2 macrophages are also metabolically distinct. In mammals, M1 macrophages show metabolic reprogramming toward glycolysis, while M2 macrophages rely on oxidative phosphorylation to generate energy. The presence of polarized functional immune phenotypes conserved from mammals to fish led us to hypothesize that a similar metabolic reprogramming in polarized macrophages exists in carp. We studied mitochondrial function of M1 and M2 carp macrophages under basal and stressed conditions to determine oxidative capacity by real-time measurements of oxygen consumption and glycolytic capacity by measuring lactate-based acidification. In M1 macrophages, we found increased nitric oxide production and irg1 expression in addition to altered oxidative phosphorylation and glycolysis. In M2 macrophages, we found increased arginase activity, and both oxidative phosphorylation and glycolysis were similar to control macrophages. These results indicate that M1 and M2 carp macrophages show distinct metabolic signatures and indicate that metabolic reprogramming may occur in carp M1 macrophages. This immunometabolic reprogramming likely supports the inflammatory phenotype of polarized macrophages in teleost fish such as carp, similar to what has been shown in mammals.
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Affiliation(s)
- Annelieke S Wentzel
- Cell Biology and Immunology Group, Wageningen University & Research, Wageningen, Netherlands
| | - Joëlle J E Janssen
- Cell Biology and Immunology Group, Wageningen University & Research, Wageningen, Netherlands.,Human and Animal Physiology Group, Wageningen University & Research, Wageningen, Netherlands
| | - Vincent C J de Boer
- Human and Animal Physiology Group, Wageningen University & Research, Wageningen, Netherlands
| | - Wouter G van Veen
- Experimental Zoology Group, Wageningen University & Research, Wageningen, Netherlands
| | - Maria Forlenza
- Cell Biology and Immunology Group, Wageningen University & Research, Wageningen, Netherlands
| | - Geert F Wiegertjes
- Aquaculture and Fisheries Group, Wageningen University & Research, Wageningen, Netherlands
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14
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Ellison A, Zamudio K, Lips K, Muletz‐Wolz C. Temperature‐mediated shifts in salamander transcriptomic responses to the amphibian‐killing fungus. Mol Ecol 2020; 29:325-343. [DOI: 10.1111/mec.15327] [Citation(s) in RCA: 17] [Impact Index Per Article: 3.4] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/22/2019] [Revised: 11/04/2019] [Accepted: 12/03/2019] [Indexed: 12/14/2022]
Affiliation(s)
- Amy Ellison
- School of Natural Sciences Bangor University Bangor UK
| | - Kelly Zamudio
- Department of Ecology & Evolutionary Biology Cornell University Ithaca NY USA
| | - Karen Lips
- Department of Biology University of Maryland College Park MD USA
| | - Carly Muletz‐Wolz
- Department of Biology University of Maryland College Park MD USA
- Center for Conservation Genomics Smithsonian Conservation Biology Institute National Zoological Park Washington DC USA
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15
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Løken OM, Bjørgen H, Hordvik I, Koppang EO. A teleost structural analogue to the avian bursa of Fabricius. J Anat 2019; 236:798-808. [PMID: 31877586 PMCID: PMC7163591 DOI: 10.1111/joa.13147] [Citation(s) in RCA: 26] [Impact Index Per Article: 4.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Accepted: 12/03/2019] [Indexed: 01/26/2023] Open
Abstract
The bursa of Fabricius is a primary and secondary lymphoid organ considered exclusively present in birds, and studies of this structure have been vital to our current understanding of the adaptive immune system of vertebrates. In this study, we reveal substantial lymphoepithelial tissue in a previously undescribed bursa in Atlantic salmon (Salmo salar), situated caudal to the urogenital papilla of the cloaca and thus analogous to the anatomical placement of the bursa of Fabricius. We investigated three groups of Atlantic salmon at different maturational stages and characterized the structure by applying dissection, radiology, scanning electron microscopy and histological techniques, including immunohistochemistry and in situ hybridization. We found that the epithelial anlage of the salmon cloacal bursa developed into substantial lymphoepithelial tissue and subsequently regressed following sexual maturation. Such a dynamic development is also a key characteristic of the avian bursa. The presence of intraepithelial lymphocytes was concomitant with expression of the leukocyte-attracting chemokine CCL19, indicative of lymphoid organ functions. We did not observe recombination or gene conversion in salmon bursal lymphocytes at any developmental stage, indicating the absence of primary lymphoid organ functions in contrast to the bursa of Fabricius. However, the possibility of the bursa to trap both enteric and environmental antigens, combined with the presence of several antigen-presenting cells residing within the lymphoepithelium, suggest the structure has secondary lymphoid organ functions. We present the discovery of a lymphoid organ in Atlantic salmon with striking topographical similarities to that of the bursa of Fabricius in birds. In addition, the age-dependent dynamics of its lymphoepithelium suggest functions related to the maturation processes of lymphocytes.
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Affiliation(s)
- Oskar M Løken
- Section of Anatomy, Faculty of Veterinary Medicine, Norwegian University of Life Sciences, Oslo, Norway
| | - Håvard Bjørgen
- Section of Anatomy, Faculty of Veterinary Medicine, Norwegian University of Life Sciences, Oslo, Norway
| | - Ivar Hordvik
- Institute of Biology, University of Bergen, Bergen, Norway
| | - Erling O Koppang
- Section of Anatomy, Faculty of Veterinary Medicine, Norwegian University of Life Sciences, Oslo, Norway
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16
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Abstract
In this review, Rothenburg discusses the gene regulatory network and chromatin-based kinetic constraints that determine activities of transcription factors in the primary establishment of T-cell identity. T-cell development in mammals is a model for lineage choice and differentiation from multipotent stem cells. Although T-cell fate choice is promoted by signaling in the thymus through one dominant pathway, the Notch pathway, it entails a complex set of gene regulatory network and chromatin state changes even before the cells begin to express their signature feature, the clonal-specific T-cell receptors (TCRs) for antigen. This review distinguishes three developmental modules for T-cell development, which correspond to cell type specification, TCR expression and selection, and the assignment of cells to different effector types. The first is based on transcriptional regulatory network events, the second is dominated by somatic gene rearrangement and mutation and cell selection, and the third corresponds to establishing a poised state of latent regulator priming through an unknown mechanism. Interestingly, in different lineages, the third module can be deployed at variable times relative to the completion of the first two modules. This review focuses on the gene regulatory network and chromatin-based kinetic constraints that determine activities of transcription factors TCF1, GATA3, PU.1, Bcl11b, Runx1, and E proteins in the primary establishment of T-cell identity.
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Affiliation(s)
- Ellen V Rothenberg
- Division of Biology and Biological Engineering, California Institute of Technology, Pasadena, California 91125, USA
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17
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Stosik MP, Tokarz-Deptuła B, Deptuła W. Specific humoral immunity in Osteichthyes. Cent Eur J Immunol 2018; 43:335-340. [PMID: 30588178 PMCID: PMC6305611 DOI: 10.5114/ceji.2018.80054] [Citation(s) in RCA: 13] [Impact Index Per Article: 1.9] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/07/2017] [Accepted: 12/12/2017] [Indexed: 12/12/2022] Open
Abstract
The fish immune system is extremely complex and has considerable adaptive potential. In Osteichthyes, the system is formed by lymphopoietic organs which are important for the differentiation and maturation of the immune system cells. These organs include the anterior kidney (phronephros), the thymus, the spleen, the posterior kidney (mesonephros), and mucosa-associated lymphoid tissues (MALT). Apart from the lymphocytic organs and the MALT system, the immune system components include defensive cells and their products. Those identified in fish include, inter alia, monocytes/macrophages, melanomacrophages, neutrophilic granulocytes, thrombocytes, B cells, plasma cells, and T cells. The roles of the individual components of the organisation of the immune system, the organs, and lymphoid tissue as well as the constituents conditioning the innate and adaptive immunity mechanisms are considered equally important, especially in the context of functional interdependence. The progress in the exploration of the processes of specific humoral immunity in Osteichthyes and the possibilities of their practical application is increasingly promising in view of the expected need for protection of fish against diseases. The paper discusses selected issues concerning recent knowledge about haematopoiesis of B cells, plasmablasts, plasma cells, and immunoglobulins (IgM, IgD, IgT/IgZ).
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Affiliation(s)
- Michał P. Stosik
- Department of Microbiology and Genetics, Faculty of Biological Sciences, University of Zielona Gora, Zielona Gora, Poland
| | - Beata Tokarz-Deptuła
- Department of Immunology, Faculty of Biology, University of Szczecin, Szczecin, Poland
| | - Wiesław Deptuła
- Department of Microbiology, Faculty of Biology, University of Szczecin, Szczecin, Poland
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18
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Kato G, Miyazawa H, Nakayama Y, Ikari Y, Kondo H, Yamaguchi T, Sano M, Fischer U. A Novel Antigen-Sampling Cell in the Teleost Gill Epithelium With the Potential for Direct Antigen Presentation in Mucosal Tissue. Front Immunol 2018; 9:2116. [PMID: 30294324 PMCID: PMC6158387 DOI: 10.3389/fimmu.2018.02116] [Citation(s) in RCA: 23] [Impact Index Per Article: 3.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/06/2018] [Accepted: 08/28/2018] [Indexed: 01/19/2023] Open
Abstract
In mammals, M cells can take up antigens through mucosal surfaces of the gut and the respiratory tract. Since M cells are deficient of lysosomes and phagosomes, the antigens are directly delivered to the mucosa-associated lymphoid tissue (MALT) without degradation. In teleost fish, the entire body surface (gills, skin, and intestinal system) is covered by mucus; however, specific antigen-sampling cells have not yet been identified in their mucosal tissues. Here, we show that two phenotypes of antigen-sampling cells take up antigens through epithelial surfaces of the rainbow trout gill. One phenotype of antigen-sampling cells has features of monocyte/macrophage/dendritic cell-type cells; they have large vacuoles in the cytoplasm and express PTPRC (CD45), CD83, IL-1β, and IL-12p40b. The second phenotype exhibits similar characteristics to mammalian M cells; the corresponding cells bind the lectin UEA-1 but not WGA and show expression of M cell marker gene Anxa5. In contrast to mammalian M cells, teleost M-type cells were found to exhibit small vacuoles in their cytoplasm and to express almost all genes related to the “phagosome”, “lysosome,” and “antigen processing and presentation” pathways. Furthermore, MHC class II was constitutively expressed on a fraction of M-type cells, and this expression was significantly increased after antigen uptake, suggesting that the MHC class II is inducible by antigen stimulation. Here, we suggest that teleost M-type cells play a role in the phylogenetically primitive teleost immune system, similar to bona-fide M cells. In addition, the presence of MHC class II expression suggests an additional role in antigen presentation in the gills, which are an organ with high T cell abundance, especially in interbranchial lymphoid tissue. The present results suggest an unconventional antigen presentation mechanism in the primitive mucosal immune system of teleosts, which generally lack highly organized lymphoid tissues. Moreover, the results of this work may be valuable for the development of mucosal vaccines that specifically target M-type cells; mucosal vaccines significantly reduce working costs and the stress that is usually induced by vaccination via injection of individual fish.
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Affiliation(s)
- Goshi Kato
- Department of Marine Biosciences, Tokyo University of Marine Science and Technology, Tokyo, Japan
| | - Haruya Miyazawa
- Department of Marine Biosciences, Tokyo University of Marine Science and Technology, Tokyo, Japan
| | - Yumiko Nakayama
- Department of Marine Biosciences, Tokyo University of Marine Science and Technology, Tokyo, Japan
| | - Yuki Ikari
- Department of Marine Biosciences, Tokyo University of Marine Science and Technology, Tokyo, Japan
| | - Hidehiro Kondo
- Department of Marine Biosciences, Tokyo University of Marine Science and Technology, Tokyo, Japan
| | - Takuya Yamaguchi
- Institute of Infectology, Friedrich-Loeffler-Institute, Federal Research Institute for Animal Health, Greifswald-Insel Riems, Germany
| | - Motohiko Sano
- Department of Marine Biosciences, Tokyo University of Marine Science and Technology, Tokyo, Japan
| | - Uwe Fischer
- Institute of Infectology, Friedrich-Loeffler-Institute, Federal Research Institute for Animal Health, Greifswald-Insel Riems, Germany
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19
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Muscle transcriptome resource for growth, lipid metabolism and immune system in Hilsa shad, Tenualosa ilisha. Genes Genomics 2018; 41:1-15. [PMID: 30196475 DOI: 10.1007/s13258-018-0732-y] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/21/2017] [Accepted: 08/22/2018] [Indexed: 12/17/2022]
Abstract
The information on the genes involved in muscle growth, lipid metabolism and immune systems would help to understand the mechanisms during the spawning migration in Hilsa shad, which in turn would be useful in its future domestication process. The primary objective of this study was to generate the transcriptome profile of its muscle through RNA seq. The total RNA was isolated and library was prepared from muscle tissue of Tenualosa ilisha, which was collected from Padma River at Farakka, India. The prepared library was then sequenced by Illumina HiSeq platform, HiSeq 2000, using paired-end strategy. A total of 8.68 GB of pair-end reads of muscle transcriptome was generated, and 43,384,267 pair-end reads were assembled into 3,04,233 contigs, of which 23.99% of assembled contigs has length ≥ 150 bp. The total GO terms were categorised into cellular component, molecular function and biological process through PANTHER database. Fifty-three genes related to muscle growth were identified and genes in different pathways were: 75 in PI3/AKT, 46 in mTOR, 76 in MAPK signalling, 24 in Janus kinase-signal transducer and activator of transcription, 45 in AMPK and 27 in cGMP pathways. This study also mined the genes involved in lipid metabolism, in which glycerophospholipid metabolism contained highest number of genes (32) and four were found to be involved in fatty acid biosynthesis. There were 58 immune related genes found, in which 31 were under innate and 27 under adaptive immunity. The present study included a large genomic resource of T. ilisha muscle generated through RNAseq, which revealed the essential dataset for our understanding of regulatory processes, specifically during the seasonal spawning migration. As Hilsa is a slow growing fish, the genes identified for muscle growth provided the basic information to study myogenesis. In addition, genes identified for lipid metabolism and immune system would provide resources for lipid synthesis and understanding of Hilsa defense mechanisms, respectively.
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20
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Abstract
The adaptive immune system arose 500 million years ago in ectothermic (cold-blooded) vertebrates. Classically, the adaptive immune system has been defined by the presence of lymphocytes expressing recombination-activating gene (RAG)-dependent antigen receptors and the MHC. These features are found in all jawed vertebrates, including cartilaginous and bony fish, amphibians and reptiles and are most likely also found in the oldest class of jawed vertebrates, the extinct placoderms. However, with the discovery of an adaptive immune system in jawless fish based on an entirely different set of antigen receptors - the variable lymphocyte receptors - the divergence of T and B cells, and perhaps innate-like lymphocytes, goes back to the origin of all vertebrates. This Review explores how recent developments in comparative immunology have furthered our understanding of the origins and function of the adaptive immune system.
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Affiliation(s)
- Martin F Flajnik
- Department of Microbiology and Immunology, University of Maryland Baltimore, Baltimore, MD, USA.
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21
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Tafalla C, Granja AG. Novel Insights on the Regulation of B Cell Functionality by Members of the Tumor Necrosis Factor Superfamily in Jawed Fish. Front Immunol 2018; 9:1285. [PMID: 29930556 PMCID: PMC6001812 DOI: 10.3389/fimmu.2018.01285] [Citation(s) in RCA: 26] [Impact Index Per Article: 3.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/05/2018] [Accepted: 05/22/2018] [Indexed: 12/12/2022] Open
Abstract
Most ligands and receptors from the tumor necrosis factor (TNF) superfamily play very important roles in the immune system. In particular, many of these molecules are essential in the regulation of B cell biology and B cell-mediated immune responses. Hence, in mammals, it is known that many TNF family members play a key role on B cell development, maturation, homeostasis, activation, and differentiation, also influencing the ability of B cells to present antigens or act as regulators of immune responses. Evolutionarily, jawed fish (including cartilaginous and bony fish) constitute the first animal group in which an adaptive immune response based on B cells and immunoglobulins is present. However, until recently, not much was known about the expression of TNF ligands and receptors in these species. The sequences of many members of the TNF superfamily have been recently identified in different species of jawed fish, thus allowing posterior analysis on the role that these ligands and receptors have on B cell functionality. In this review, we summarize the current knowledge on the impact that the TNF family members have in different aspects of B cell functionality in fish, also providing an in depth comparison with functional aspects of TNF members in mammals, that will permit a further understanding of how B cell functionality is regulated in these distant animal groups.
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Affiliation(s)
| | - Aitor G Granja
- Animal Health Research Center (CISA-INIA), Madrid, Spain
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22
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Neely HR, Guo J, Flowers EM, Criscitiello MF, Flajnik MF. "Double-duty" conventional dendritic cells in the amphibian Xenopus as the prototype for antigen presentation to B cells. Eur J Immunol 2018; 48:430-440. [PMID: 29235109 DOI: 10.1002/eji.201747260] [Citation(s) in RCA: 28] [Impact Index Per Article: 4.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/02/2017] [Revised: 10/20/2017] [Accepted: 12/07/2017] [Indexed: 12/19/2022]
Abstract
Two populations of dendritic cells (DCs) are found in mammals, one derived from hematopoietic precursors (conventional/cDC), and another derived from mesenchymal precursors, the follicular DC (FDC); the latter is specialized for antigen presentation to B cells, and has only been definitively demonstrated in mammals. Both cDC and FDC are necessary for induction of germinal centers (GC) and GC-dependent class switch recombination (CSR) and somatic hypermutation (SHM). We demonstrate that in Xenopus, an amphibian in which immunoglobulin CSR and SHM occur without GC formation, a single type of DC has properties of both cDC and FDC, including high expression of MHC class II for the former and display of native antigen at the cell surface for the latter. Our data confirm that the advent of FDC functionality preceded emergence of bona fide FDC, which was in turn crucial for the development of GC formation and efficient affinity maturation in mammals.
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Affiliation(s)
- Harold R Neely
- Department of Microbiology and Immunology, University of Maryland Baltimore, Baltimore, MD, USA.,Department of Microbiology and Immunobiology, Harvard Medical School, Boston, MA, USA
| | - Jacqueline Guo
- Department of Microbiology and Immunology, University of Maryland Baltimore, Baltimore, MD, USA
| | - Emily M Flowers
- Department of Microbiology and Immunology, University of Maryland Baltimore, Baltimore, MD, USA
| | | | - Martin F Flajnik
- Department of Microbiology and Immunology, University of Maryland Baltimore, Baltimore, MD, USA
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23
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Patrikainen MS, Tolvanen MEE, Aspatwar A, Barker HR, Ortutay C, Jänis J, Laitaoja M, Hytönen VP, Azizi L, Manandhar P, Jáger E, Vullo D, Kukkurainen S, Hilvo M, Supuran CT, Parkkila S. Identification and characterization of a novel zebrafish ( Danio rerio) pentraxin-carbonic anhydrase. PeerJ 2017; 5:e4128. [PMID: 29230365 PMCID: PMC5723433 DOI: 10.7717/peerj.4128] [Citation(s) in RCA: 7] [Impact Index Per Article: 0.9] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/30/2017] [Accepted: 11/14/2017] [Indexed: 12/29/2022] Open
Abstract
Background Carbonic anhydrases (CAs) are ubiquitous, essential enzymes which catalyze the conversion of carbon dioxide and water to bicarbonate and H+ ions. Vertebrate genomes generally contain gene loci for 15–21 different CA isoforms, three of which are enzymatically inactive. CA VI is the only secretory protein of the enzymatically active isoforms. We discovered that non-mammalian CA VI contains a C-terminal pentraxin (PTX) domain, a novel combination for both CAs and PTXs. Methods We isolated and sequenced zebrafish (Danio rerio) CA VI cDNA, complete with the sequence coding for the PTX domain, and produced the recombinant CA VI–PTX protein. Enzymatic activity and kinetic parameters were measured with a stopped-flow instrument. Mass spectrometry, analytical gel filtration and dynamic light scattering were used for biophysical characterization. Sequence analyses and Bayesian phylogenetics were used in generating hypotheses of protein structure and CA VI gene evolution. A CA VI–PTX antiserum was produced, and the expression of CA VI protein was studied by immunohistochemistry. A knock-down zebrafish model was constructed, and larvae were observed up to five days post-fertilization (dpf). The expression of ca6 mRNA was quantitated by qRT-PCR in different developmental times in morphant and wild-type larvae and in different adult fish tissues. Finally, the swimming behavior of the morphant fish was compared to that of wild-type fish. Results The recombinant enzyme has a very high carbonate dehydratase activity. Sequencing confirms a 530-residue protein identical to one of the predicted proteins in the Ensembl database (ensembl.org). The protein is pentameric in solution, as studied by gel filtration and light scattering, presumably joined by the PTX domains. Mass spectrometry confirms the predicted signal peptide cleavage and disulfides, and N-glycosylation in two of the four observed glycosylation motifs. Molecular modeling of the pentamer is consistent with the modifications observed in mass spectrometry. Phylogenetics and sequence analyses provide a consistent hypothesis of the evolutionary history of domains associated with CA VI in mammals and non-mammals. Briefly, the evidence suggests that ancestral CA VI was a transmembrane protein, the exon coding for the cytoplasmic domain was replaced by one coding for PTX domain, and finally, in the therian lineage, the PTX-coding exon was lost. We knocked down CA VI expression in zebrafish embryos with antisense morpholino oligonucleotides, resulting in phenotype features of decreased buoyancy and swim bladder deflation in 4 dpf larvae. Discussion These findings provide novel insights into the evolution, structure, and function of this unique CA form.
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Affiliation(s)
| | | | - Ashok Aspatwar
- Faculty of Medicine and Life Sciences, University of Tampere, Tampere, Finland.,Fimlab Ltd., Tampere University Hospital, Tampere, Finland
| | - Harlan R Barker
- Faculty of Medicine and Life Sciences, University of Tampere, Tampere, Finland
| | | | - Janne Jänis
- Department of Chemistry, University of Eastern Finland, Joensuu, Finland
| | - Mikko Laitaoja
- Department of Chemistry, University of Eastern Finland, Joensuu, Finland
| | - Vesa P Hytönen
- Faculty of Medicine and Life Sciences, University of Tampere, Tampere, Finland.,Fimlab Ltd., Tampere University Hospital, Tampere, Finland
| | - Latifeh Azizi
- Faculty of Medicine and Life Sciences, University of Tampere, Tampere, Finland
| | - Prajwol Manandhar
- Faculty of Medicine and Life Sciences, University of Tampere, Tampere, Finland.,Center for Molecular Dynamics Nepal, Kathmandu, Nepal
| | - Edit Jáger
- Department of Epidemiology, Faculty of Health Sciences, Semmelweis University, Budapest, Hungary
| | - Daniela Vullo
- Dipartimento Neurofarba, Sezione di Scienze Farmaceutiche e Nutraceutiche, Università degli Studi di Firenze, Florence, Italy
| | - Sampo Kukkurainen
- Faculty of Medicine and Life Sciences, University of Tampere, Tampere, Finland
| | - Mika Hilvo
- Faculty of Medicine and Life Sciences, University of Tampere, Tampere, Finland.,Zora Biosciences Ltd., Espoo, Finland
| | - Claudiu T Supuran
- Dipartimento Neurofarba, Sezione di Scienze Farmaceutiche e Nutraceutiche, Università degli Studi di Firenze, Florence, Italy
| | - Seppo Parkkila
- Faculty of Medicine and Life Sciences, University of Tampere, Tampere, Finland.,Fimlab Ltd., Tampere University Hospital, Tampere, Finland
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24
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Abstract
Host-microbe interactions are influenced by complex host genetics and environment. Studies across animal taxa have aided our understanding of how intestinal microbiota influence vertebrate development, disease, and physiology. However, traditional mammalian studies can be limited by the use of isogenic strains, husbandry constraints that result in small sample sizes and limited statistical power, reliance on indirect characterization of gut microbial communities from fecal samples, and concerns of whether observations in artificial conditions are actually reflective of what occurs in the wild. Fish models are able to overcome many of these limitations. The extensive variation in the physiology, ecology, and natural history of fish enriches studies of the evolution and ecology of host-microbe interactions. They share physiological and immunological features common among vertebrates, including humans, and harbor complex gut microbiota, which allows identification of the mechanisms driving microbial community assembly. Their accelerated life cycles and large clutch sizes and the ease of sampling both internal and external microbial communities make them particularly well suited for robust statistical studies of microbial diversity. Gnotobiotic techniques, genetic manipulation of the microbiota and host, and transparent juveniles enable novel insights into mechanisms underlying development of the digestive tract and disease states. Many diseases involve a complex combination of genes which are difficult to manipulate in homogeneous model organisms. By taking advantage of the natural genetic variation found in wild fish populations, as well as of the availability of powerful genetic tools, future studies should be able to identify conserved genes and pathways that contribute to human genetic diseases characterized by dysbiosis.
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Affiliation(s)
- Emily A Lescak
- University of Alaska Anchorage, Department of Biological Sciences, Anchorage, Alaska, USA
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25
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Mashoof S, Criscitiello MF. Fish Immunoglobulins. BIOLOGY 2016; 5:E45. [PMID: 27879632 PMCID: PMC5192425 DOI: 10.3390/biology5040045] [Citation(s) in RCA: 117] [Impact Index Per Article: 13.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 10/09/2016] [Revised: 11/03/2016] [Accepted: 11/09/2016] [Indexed: 01/19/2023]
Abstract
The B cell receptor and secreted antibody are at the nexus of humoral adaptive immunity. In this review, we summarize what is known of the immunoglobulin genes of jawed cartilaginous and bony fishes. We focus on what has been learned from genomic or cDNA sequence data, but where appropriate draw upon protein, immunization, affinity and structural studies. Work from major aquatic model organisms and less studied comparative species are both included to define what is the rule for an immunoglobulin isotype or taxonomic group and what exemplifies an exception.
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Affiliation(s)
- Sara Mashoof
- Comparative Immunogenetics Laboratory, Department of Veterinary Pathobiology, College of Veterinary Medicine and Biomedical Sciences, Texas A&M University, College Station, TX 77843, USA.
| | - Michael F Criscitiello
- Comparative Immunogenetics Laboratory, Department of Veterinary Pathobiology, College of Veterinary Medicine and Biomedical Sciences, Texas A&M University, College Station, TX 77843, USA.
- Department of Microbial Pathogenesis and Immunology, College of Medicine, Texas A&M University, College Station, TX 77807, USA.
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Weir H, Chen PL, Deiss TC, Jacobs N, Nabity MB, Young M, Criscitiello MF. DNP-KLH Yields Changes in Leukocyte Populations and Immunoglobulin Isotype Use with Different Immunization Routes in Zebrafish. Front Immunol 2015; 6:606. [PMID: 26648935 PMCID: PMC4664633 DOI: 10.3389/fimmu.2015.00606] [Citation(s) in RCA: 9] [Impact Index Per Article: 0.9] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/16/2015] [Accepted: 11/13/2015] [Indexed: 01/22/2023] Open
Abstract
Distinct methods are required for inducing mucosal versus systemic immunity in mammals for vaccine protection at the tissues most commonly breached by pathogens. Understanding of mucosal immunization in teleost fish is needed to combat aquaculture disease, understand emerging ecological threats, and know how vertebrate adaptive immunity evolved. Here, we quantitatively measured expression levels of IgM as well as the teleost mucosal immunoglobulin, IgZ/IgT, in zebrafish given an antigen systemically via intraperitoneal (i.p.) injection or mucosally via bath immersion. Both immunoglobulin isotypes and the B cell activating factor gene transcription was induced in fish injected with antigen as compared to saline injected or antigen immersed fish, though these failed to reach statistical significance. Here we provide additional reference hematology for this model species. Differential blood counts revealed a greater lymphocyte percentage in both i.p. and immersed fish, with increase in large lymphocyte counts and decrease in neutrophils. These humoral adaptive gene transcription and cytological data should provide a foundation for more studies connecting immunology in this dominant developmental and genetic fish model to other species where mucosal immunization is of greater commercial importance.
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Affiliation(s)
- Heather Weir
- Comparative Immunogenetics Laboratory, College of Veterinary Medicine and Biomedical Sciences, Texas A&M University , College Station, TX , USA ; Department of Veterinary Pathobiology, College of Veterinary Medicine and Biomedical Sciences, Texas A&M University , College Station, TX , USA ; Department of Science, A&M Consolidated High School , College Station, TX , USA
| | - Patricia L Chen
- Comparative Immunogenetics Laboratory, College of Veterinary Medicine and Biomedical Sciences, Texas A&M University , College Station, TX , USA ; Department of Veterinary Pathobiology, College of Veterinary Medicine and Biomedical Sciences, Texas A&M University , College Station, TX , USA
| | - Thaddeus C Deiss
- Comparative Immunogenetics Laboratory, College of Veterinary Medicine and Biomedical Sciences, Texas A&M University , College Station, TX , USA ; Department of Veterinary Pathobiology, College of Veterinary Medicine and Biomedical Sciences, Texas A&M University , College Station, TX , USA
| | - Natalie Jacobs
- Comparative Immunogenetics Laboratory, College of Veterinary Medicine and Biomedical Sciences, Texas A&M University , College Station, TX , USA ; Department of Veterinary Pathobiology, College of Veterinary Medicine and Biomedical Sciences, Texas A&M University , College Station, TX , USA
| | - Mary B Nabity
- Department of Veterinary Pathobiology, College of Veterinary Medicine and Biomedical Sciences, Texas A&M University , College Station, TX , USA
| | - Matt Young
- Comparative Immunogenetics Laboratory, College of Veterinary Medicine and Biomedical Sciences, Texas A&M University , College Station, TX , USA ; Department of Veterinary Pathobiology, College of Veterinary Medicine and Biomedical Sciences, Texas A&M University , College Station, TX , USA ; Department of Science, A&M Consolidated High School , College Station, TX , USA
| | - Michael F Criscitiello
- Comparative Immunogenetics Laboratory, College of Veterinary Medicine and Biomedical Sciences, Texas A&M University , College Station, TX , USA ; Department of Veterinary Pathobiology, College of Veterinary Medicine and Biomedical Sciences, Texas A&M University , College Station, TX , USA
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27
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Pettinello R, Dooley H. The immunoglobulins of cold-blooded vertebrates. Biomolecules 2014; 4:1045-69. [PMID: 25427250 PMCID: PMC4279169 DOI: 10.3390/biom4041045] [Citation(s) in RCA: 49] [Impact Index Per Article: 4.5] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/28/2014] [Revised: 11/10/2014] [Accepted: 11/13/2014] [Indexed: 12/27/2022] Open
Abstract
Although lymphocyte-like cells secreting somatically-recombining receptors have been identified in the jawless fishes (hagfish and lamprey), the cartilaginous fishes (sharks, skates, rays and chimaera) are the most phylogenetically distant group relative to mammals in which bona fide immunoglobulins (Igs) have been found. Studies of the antibodies and humoral immune responses of cartilaginous fishes and other cold-blooded vertebrates (bony fishes, amphibians and reptiles) are not only revealing information about the emergence and roles of the different Ig heavy and light chain isotypes, but also the evolution of specialised adaptive features such as isotype switching, somatic hypermutation and affinity maturation. It is becoming increasingly apparent that while the adaptive immune response in these vertebrate lineages arose a long time ago, it is most definitely not primitive and has evolved to become complex and sophisticated. This review will summarise what is currently known about the immunoglobulins of cold-blooded vertebrates and highlight the differences, and commonalities, between these and more “conventional” mammalian species.
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Affiliation(s)
- Rita Pettinello
- School of Biological Sciences, University of Aberdeen, Aberdeen AB24 2TZ, UK.
| | - Helen Dooley
- School of Biological Sciences, University of Aberdeen, Aberdeen AB24 2TZ, UK.
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Vetvicka V, Vannucci L, Sima P. The Effects of β - Glucan on Fish Immunity. NORTH AMERICAN JOURNAL OF MEDICAL SCIENCES 2014; 5:580-8. [PMID: 24350069 PMCID: PMC3842698 DOI: 10.4103/1947-2714.120792] [Citation(s) in RCA: 65] [Impact Index Per Article: 5.9] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Indexed: 11/04/2022]
Abstract
Administration of glucans through immersion, dietary inclusion or injection has been found to enhance many types of immune responses, resistance to bacterial and viral infections and to environmental stress in many fish species. Although the efficacy of the glucan varies with types and administration, glucan used as an immunomodulatory and mostly immunostimulatory additive has been found satisfactory in eliciting immunity in commercial aquaculture. Development of more efficient administration methods will facilitate the routine and prophylactic use of glucans as natural immunostimulants of fish. Using a PubMed search, this review has an extensive literature on glucan in fish immunity.
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Affiliation(s)
- Vaclav Vetvicka
- Department of Pathology, University of Louisville, Louisville, KY 40202, USA
| | - Luca Vannucci
- Department of Immunology, Institute of Microbiology, Prague, Czech Republic
| | - Petr Sima
- Department of Immunology, Institute of Microbiology, Prague, Czech Republic
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29
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Lympho-granulocytic tissue associated with the wall of the spiral valve in the African lungfish Protopterus annectens. Cell Tissue Res 2013; 355:397-407. [PMID: 24253466 DOI: 10.1007/s00441-013-1746-z] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/22/2013] [Accepted: 10/14/2013] [Indexed: 10/26/2022]
Abstract
We describe the structure of the lympho-granulocytic tissue associated with the wall of the spiral valve of the African lungfish Protopterus annectens. The study was performed under freshwater conditions and after 6 months of aestivation. The lympho-granulocytic tissue consists of nodes surrounded by reticular tissue. The nodes are formed by an outer and an inner component separated by a thin collagenous layer. The outer component is a reticular-like tissue that contains two types of granulocytes, developing and mature plasma cells and melanomacrophage centres (MMCs). The inner component, the parenchyma, contains a meshwork of trabeculae and vascular sinusoids and shows dark and pale areas. The dark areas contain diffuse lymphoid tissue, with a large number of mitoses and plasma cell clusters. The pale areas contain a small number of macrophages and lymphocytes. Macrophages and sinus endothelial cells are filled with haemosiderin granules and appear to form part of the reticuloendothelial system of the lungfish. The reticular tissue houses granulocytes, plasma cells and MMCs and might serve for the housing and maturation of cells of the white series. After aestivation, the nodes undergo lymphocyte depletion, the suppression of mitosis, granulocyte invasion and the occurrence of cell death. By contrast, few histological changes occur in the reticular tissue. Whereas the nodes appear to be involved in lymphocyte proliferation and plasma cell maturation, the function of the reticular tissue remains obscure.
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30
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Fischer U, Koppang EO, Nakanishi T. Teleost T and NK cell immunity. FISH & SHELLFISH IMMUNOLOGY 2013; 35:197-206. [PMID: 23664867 DOI: 10.1016/j.fsi.2013.04.018] [Citation(s) in RCA: 102] [Impact Index Per Article: 8.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Received: 10/26/2012] [Revised: 02/01/2013] [Accepted: 04/12/2013] [Indexed: 06/02/2023]
Abstract
The main function of the immune system is to maintain the organism's homeostasis when invaded by foreign material or organisms. Prior to successful elimination of the invader it is crucial to distinguish self from non-self. Most pathogens and altered cells can be recognized by immune cells through expressed pathogen- or danger-associated molecular patterns (PAMPS or DAMPS, respectively), through non-self (e.g. allogenic or xenogenic cells) or missing major histocompatibility (MHC) class I molecules (some virus-infected target cells), and by presenting foreign non-self peptides of intracellular (through MHC class I-e.g. virus-infected target cells) or extracellular (through MHC class II-e.g. from bacteria) origin. In order to eliminate invaders directly or by destroying their ability to replicate (e.g. virus-infected cells) specialized immune cells of the innate and adaptive responses appeared during evolution. The first line of defence is represented by the evolutionarily ancient macrophages and natural killer (NK) cells. These innate mechanisms are well developed in bony fish. Two types of NK cell homologues have been described in fish: non-specific cytotoxic cells and NK-like cells. Adaptive cell-mediated cytotoxicity (CMC) requires key molecules expressed on cytotoxic T lymphocytes (CTLs) and target cells. CTLs kill host cells harbouring intracellular pathogens by binding of their T cell receptor (TCR) and its co-receptor CD8 to a complex of MHC class I and bound peptide on the infected host cell. Alternatively, extracellular antigens are taken up by professional antigen presenting cells such as macrophages, dendritic cells and B cells to process those antigens and present the resulting peptides in association with MHC class II to CD4(+) T helper cells. During recent years, genes encoding MHC class I and II, TCR and its co-receptors CD8 and CD4 have been cloned in several fish species and antibodies have been developed to study protein expression in morphological and functional contexts. Functional assays for innate and adaptive lymphocyte responses have been developed in only a few fish species. This review summarizes and discusses recent results and developments in the field of T and NK cell responses with focus on economically important and experimental model fish species in the context of vaccination.
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Affiliation(s)
- Uwe Fischer
- Friedrich-Loeffler-Institut, Federal Research Institute for Animal Health, Institute of Infectology, Suedufer 10, 17493 Greifswald-Insel Riems, Germany.
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31
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Sunyer JO. Fishing for mammalian paradigms in the teleost immune system. Nat Immunol 2013; 14:320-6. [PMID: 23507645 PMCID: PMC4203445 DOI: 10.1038/ni.2549] [Citation(s) in RCA: 180] [Impact Index Per Article: 15.0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/05/2012] [Accepted: 01/17/2013] [Indexed: 02/06/2023]
Abstract
Recent years have witnessed a renaissance in the study of fish immune systems. Such studies have greatly expanded the knowledge of the evolution and diversification of vertebrate immune systems. Several findings in those studies have overturned old paradigms about the immune system and led to the discovery of novel aspects of mammalian immunity. Here I focus on how findings pertaining to immunity in teleost (bony) fish have led to major new insights about mammalian B cell function in innate and adaptive immunity. Additionally, I illustrate how the discovery of the most ancient mucosal immunoglobulin described thus far will help resolve unsettled paradigms of mammalian mucosal immunity.
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Affiliation(s)
- J Oriol Sunyer
- Department of Pathobiology, School of Veterinary Medicine, University of Pennsylvania, Philadelphia, Pennsylvania, USA.
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32
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L⊘kka G, Austb⊘ L, Falk K, Bjerkås I, Koppang EO. Intestinal morphology of the wild atlantic salmon (Salmo salar). J Morphol 2013; 274:859-76. [DOI: 10.1002/jmor.20142] [Citation(s) in RCA: 62] [Impact Index Per Article: 5.2] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/13/2012] [Revised: 01/08/2013] [Accepted: 01/23/2013] [Indexed: 12/11/2022]
Affiliation(s)
- Guro L⊘kka
- Department of Basic Sciences and Aquatic Medicine; Norwegian School of Veterinary Science; Oslo; Norway
| | - Lars Austb⊘
- Department of Basic Sciences and Aquatic Medicine; Norwegian School of Veterinary Science; Oslo; Norway
| | - Knut Falk
- Department of Laboratory Services; National Veterinary Institute; Oslo; Norway
| | - Inge Bjerkås
- Department of Basic Sciences and Aquatic Medicine; Norwegian School of Veterinary Science; Oslo; Norway
| | - Erling Olaf Koppang
- Department of Basic Sciences and Aquatic Medicine; Norwegian School of Veterinary Science; Oslo; Norway
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33
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Ge Q, Zhao Y. Evolution of thymus organogenesis. DEVELOPMENTAL AND COMPARATIVE IMMUNOLOGY 2013; 39:85-90. [PMID: 22266420 DOI: 10.1016/j.dci.2012.01.002] [Citation(s) in RCA: 18] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Received: 12/08/2011] [Revised: 01/06/2012] [Accepted: 01/06/2012] [Indexed: 05/31/2023]
Abstract
The thymus is the primary organ for functional T lymphocyte development in jawed vertebrates. A new study in the jawless fish, lampreys, indicates the existence of a primitive thymus in these surviving representatives of the most ancient vertebrates, providing strong evidence of co-evolution of T cells and thymus. This review summarizes the wealth of data that have been generated towards understanding the evolution of the thymus in the vertebrates. Progress in identifying genetic networks and cellular mechanisms that control thymus organogenesis in mammals and their evolution in lower species may inspire the development of new strategies for medical interventions targeting faulty thymus functions.
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Affiliation(s)
- Qing Ge
- Key Laboratory of Medical Immunology, Ministry of Health, Department of Immunology, School of Basic Medical Sciences, Peking University Health Science Center, 38 Xue Yuan Road, Beijing 100191, PR China.
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34
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Arciuli M, Fiocco D, Cicero R, Maida I, Zanna PT, Guida G, Horsberg TE, Koppang EO, Gallone A. Melanogenesis in visceral tissues ofSalmo salar. A link between immunity and pigment production? Biochem Cell Biol 2012. [DOI: 10.1139/o2012-033] [Citation(s) in RCA: 11] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/22/2022] Open
Abstract
Melanogenesis is mostly studied in melanocytes and melanoma cells, but much less is known about other pigment cell systems. Liver, spleen, kidney, and other organs of lower vertebrates harbour a visceral pigment cell system with an embryonic origin that differs from that of melanocytes. In teleosts, melanin-containing cells occur in the reticulo-endothelial system and are mainly in the kidney and spleen. The Atlantic salmon ( Salmo salar L.) is an ichthyic breeding species of considerable economic importance. The accumulation of pigments in salmon visceral organs and musculature adversely affects the quality of fish products and is a problem for the aquaculture industry. With the aim to reveal novel functions and behaviour of the salmonid extracutaneous pigment system, we investigated aspects of the melanogenic systems in the tissues of Atlantic salmon, as well as in SHK-1 cells, which is a long-term cell line derived from macrophages of the Atlantic salmon head-kidney. We demonstrate that a melanogenic system is present in SHK-1 cells, head-kidney, and spleen tissues. As teleosts lack lymph nodes and Peyer’s patches, the head-kidney and spleen are regarded as the most important secondary lymphoid organs. The detection of tyrosinase activity in lymphoid organs indicates that a link exists between the extracutaneous pigmentary system and the immune system in salmon.
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Affiliation(s)
- Marcella Arciuli
- Sezione di Biologia Medica, Dipartimento di Scienze Mediche di Base, Neuroscienze ed Organi di Senso, Università degli Studi di Bari, Policlinico-Piazza Giulio Cesare, 70124 Bari, Italy
| | - Daniela Fiocco
- Dipartimento di Medicina Clinica e Sperimentale, Università degli Studi di Foggia, Viale Pinto 1, 71122 Foggia, Italy
| | - Rosina Cicero
- Sezione di Biologia Medica, Dipartimento di Scienze Mediche di Base, Neuroscienze ed Organi di Senso, Università degli Studi di Bari, Policlinico-Piazza Giulio Cesare, 70124 Bari, Italy
| | - Immacolata Maida
- Sezione di Biologia Medica, Dipartimento di Scienze Mediche di Base, Neuroscienze ed Organi di Senso, Università degli Studi di Bari, Policlinico-Piazza Giulio Cesare, 70124 Bari, Italy
| | - Paola T. Zanna
- Sezione di Biologia Medica, Dipartimento di Scienze Mediche di Base, Neuroscienze ed Organi di Senso, Università degli Studi di Bari, Policlinico-Piazza Giulio Cesare, 70124 Bari, Italy
| | - Gabriella Guida
- Sezione di Biologia Medica, Dipartimento di Scienze Mediche di Base, Neuroscienze ed Organi di Senso, Università degli Studi di Bari, Policlinico-Piazza Giulio Cesare, 70124 Bari, Italy
| | - Tor E. Horsberg
- Section of Pharmacology and Toxicology, Department of Food Safety & Infection Biology, Norwegian School of Veterinary Science, Ullevålsveien 72, Box 8146 Dep, Oslo, Norway
| | - Erling O. Koppang
- Section of Anatomy and Pathology, Department of Basic Sciences & Aquatic Medicine, Norwegian School of Veterinary Science, Ullevålsveien 72, Box 8146 Dep, 0033 Oslo, Norway
| | - Anna Gallone
- Sezione di Biologia Medica, Dipartimento di Scienze Mediche di Base, Neuroscienze ed Organi di Senso, Università degli Studi di Bari, Policlinico-Piazza Giulio Cesare, 70124 Bari, Italy
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35
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Rauta PR, Nayak B, Das S. Immune system and immune responses in fish and their role in comparative immunity study: a model for higher organisms. Immunol Lett 2012; 148:23-33. [PMID: 22902399 DOI: 10.1016/j.imlet.2012.08.003] [Citation(s) in RCA: 278] [Impact Index Per Article: 21.4] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/03/2012] [Revised: 08/01/2012] [Accepted: 08/03/2012] [Indexed: 12/16/2022]
Abstract
The basal position of fish in vertebrate phylogeny makes them very attractive for genomic and functional comparative immunity studies. Adaptive immunity arose early in vertebrate evolution, 450 million years ago between the divergence of cyclostomes and cartilaginous fish. The fundamental immune molecules, which include Ag-recognizing lymphocytes, immunoglobulins (Abs and Ig-family TCR), MHC products, and recombination-activating (RAG) 1 and 2 genes and the recombination mechanisms (cause of diversity in TCRs and Igs) are similar in fish and mammals. These molecules and their immune response mechanisms unravelled the primordial vertebrate immune system repertoire and adaptive radiations. Moreover, screening of animal models like zebrafish has a great importance to discover genes involved in T cell development, thymic organogenesis, and in immunity to infections. The zebrafish model may also be useful for cancer research due to its various features like rapid development, tractable genetics, ease in in vivo imaging and chemical screening.
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Affiliation(s)
- Pradipta R Rauta
- Department of Life Science, National Institute of Technology, Rourkela 769008, Odisha, India
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36
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The spleen of the African lungfish Protopterus annectens: freshwater and aestivation. Cell Tissue Res 2012; 350:143-56. [DOI: 10.1007/s00441-012-1462-0] [Citation(s) in RCA: 7] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/06/2012] [Accepted: 05/31/2012] [Indexed: 10/28/2022]
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37
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Boehm T, Hess I, Swann JB. Evolution of lymphoid tissues. Trends Immunol 2012; 33:315-21. [PMID: 22483556 DOI: 10.1016/j.it.2012.02.005] [Citation(s) in RCA: 75] [Impact Index Per Article: 5.8] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/05/2011] [Revised: 02/16/2012] [Accepted: 02/16/2012] [Indexed: 01/04/2023]
Abstract
Lymphoid organs are integral parts of all vertebrate adaptive immune systems. Primary lymphoid tissues exhibit a remarkable functional dichotomy: T cells develop in specialized thymopoietic tissues located in the pharynx, whereas B cells develop in distinct areas of general hematopoietic areas, such as the kidney or bone marrow. Among secondary lymphoid tissues, the spleen is present in all vertebrates, whereas lymph nodes represent an innovation particular to mammals and some birds. A comparative analysis of anatomical, functional and genomic features thus reveals the core components of adaptive immune systems. Such information has guided recent attempts at reconstructing lymphopoietic functions in vivo and in the future might inspire the development of new strategies for medical interventions restoring and modulating immune functions.
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Affiliation(s)
- Thomas Boehm
- Department of Developmental Immunology, Max Planck Institute of Immunobiology and Epigenetics, Stuebeweg 51, D-79108 Freiburg, Germany.
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38
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39
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Withers DR, Gaspal FM, Bekiaris V, McConnell FM, Kim M, Anderson G, Lane PJL. OX40 and CD30 signals in CD4(+) T-cell effector and memory function: a distinct role for lymphoid tissue inducer cells in maintaining CD4(+) T-cell memory but not effector function. Immunol Rev 2012; 244:134-48. [PMID: 22017436 DOI: 10.1111/j.1600-065x.2011.01057.x] [Citation(s) in RCA: 42] [Impact Index Per Article: 3.2] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/30/2022]
Abstract
CD4(+) effector and memory T cells play a pivotal role in the development of both normal and pathogenic immune responses. This review focuses on the molecular and cellular mechanisms that regulate their development, with particular focus on the tumor necrosis factor superfamily members OX40 (TNFRSF4) and CD30 (TNFRSF8). We discuss the evidence that in mice, these molecular signaling pathways act synergistically to regulate the development of both effector and memory CD4(+) T cells but that the cells that regulate memory versus effector function are distinct, effectively allowing the independent regulation of the memory and effector CD4(+) T-cell pools.
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Affiliation(s)
- David R Withers
- MRC Centre for Immune Regulation, College of Medical and Dental Sciences, University of Birmingham, Birmingham, UK
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40
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Lane PJL, Gaspal FM, McConnell FM, Kim MY, Anderson G, Withers DR. Lymphoid tissue inducer cells: innate cells critical for CD4+ T cell memory responses? Ann N Y Acad Sci 2012; 1247:1-15. [PMID: 22260374 DOI: 10.1111/j.1749-6632.2011.06284.x] [Citation(s) in RCA: 12] [Impact Index Per Article: 0.9] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 05/02/2024]
Abstract
Lymphoid tissue inducer cells (LTi) are a relatively new arrival on the immunological cellular landscape, having first been characterized properly only 15 years ago. They are members of an emerging family of innate lymphoid cells (ILCs). Elucidation of their function reveals links not only with the ancient innate immune system, but also with adaptive immune responses, in particular the development of lymph nodes and CD4(+) T cell memory immune responses, which on one hand underpin the success of vaccination strategies, and on the other hand drive many human immunologically mediated diseases. This perspective article is not an exhaustive account of the role of LTi in the development of lymphoid tissues, as there have been many excellent reviews published already. Instead, we combine current knowledge of genetic phylogeny and comparative immunology, together with classical mouse genetics, to suggest how LTi might have evolved from a primitive lymphocytic innate cell in the ancestral 500-million-year-old vertebrate immune system into a cell critical for adaptive CD4(+) T cell immune responses in mammals.
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Affiliation(s)
- Peter J L Lane
- MRC Centre for Immune Regulation, College of Medical and Dental Sciences, University of Birmingham, UK.
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41
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Salinas I, Zhang YA, Sunyer JO. Mucosal immunoglobulins and B cells of teleost fish. DEVELOPMENTAL AND COMPARATIVE IMMUNOLOGY 2011; 35:1346-65. [PMID: 22133710 PMCID: PMC3428141 DOI: 10.1016/j.dci.2011.11.009] [Citation(s) in RCA: 393] [Impact Index Per Article: 28.1] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 05/04/2023]
Abstract
As physical barriers that separate teleost fish from the external environment, mucosae are also active immunological sites that protect them against exposure to microbes and stressors. In mammals, the sites where antigens are sampled from mucosal surfaces and where stimulation of naïve T and B lymphocytes occurs are known as inductive sites and are constituted by mucosa-associated lymphoid tissue (MALT). According to anatomical location, the MALT in teleost fish is subdivided into gut-associated lymphoid tissue (GALT), skin-associated lymphoid tissue (SALT), and gill-associated lymphoid tissue (GIALT). All MALT contain a variety of leukocytes, including, but not limited to, T cells, B cells, plasma cells, macrophages and granulocytes. Secretory immunoglobulins are produced mainly by plasmablasts and plasma cells, and play key roles in the maintenance of mucosal homeostasis. Until recently, teleost fish B cells were thought to express only two classes of immunoglobulins, IgM and IgD, in which IgM was thought to be the only one responding to pathogens both in systemic and mucosal compartments. However, a third teleost immunoglobulin class, IgT/IgZ, was discovered in 2005, and it has recently been shown to behave as the prevalent immunoglobulin in gut mucosal immune responses. The purpose of this review is to summarise the current knowledge of mucosal immunoglobulins and B cells of fish MALT. Moreover, we attempt to integrate the existing knowledge on both basic and applied research findings on fish mucosal immune responses, with the goal to provide new directions that may facilitate the development of novel vaccination strategies that stimulate not only systemic, but also mucosal immunity.
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Affiliation(s)
| | | | - J. Oriol Sunyer
- Department of Pathobiology, School of Veterinary Medicine, University of Pennsylvania, Philadelphia, PA 19104, USA
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42
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Sima P, Vetvicka V. Bioactive substances with anti-neoplastic efficacy from marine invertebrates: Porifera and Coelenterata. World J Clin Oncol 2011; 2:355-61. [PMID: 22087433 PMCID: PMC3212816 DOI: 10.5306/wjco.v2.i11.355] [Citation(s) in RCA: 12] [Impact Index Per Article: 0.9] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/06/2011] [Revised: 10/10/2011] [Accepted: 10/17/2011] [Indexed: 02/06/2023] Open
Abstract
An ever increasing demand for new lead compounds in the pharmaceutical industry has led scientists to search for natural bioactive products. Based on this extensive research, marine invertebrates now represent a rich source of novel substances with significant anti-neoplastic activities. As the current approach of synthesizing new and chemically modifying old drugs seems to have slowed down, and the identification of new anticancer drugs is not too promising, a new approach is clearly needed. The objective of this review is to present up-to-date data on these newer compounds. Based on the data summarized in this short review, it is clear that marine invertebrates represent an extremely important source of compounds with potential anti-cancer effects. Considering that we tested only a tiny number of Porifera and Coelenterata, the best is yet to come.
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Affiliation(s)
- Peter Sima
- Peter Sima, Institute of Microbiology, Czech Academy of Sciences, 142 20 Prague 15400, Czech Republic
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43
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Hsu E. The invention of lymphocytes. Curr Opin Immunol 2011; 23:156-62. [PMID: 21227671 PMCID: PMC3073649 DOI: 10.1016/j.coi.2010.12.007] [Citation(s) in RCA: 15] [Impact Index Per Article: 1.1] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/28/2010] [Revised: 12/07/2010] [Accepted: 12/13/2010] [Indexed: 11/23/2022]
Abstract
Lamprey and hagfish are surviving representatives of the most ancient vertebrates. They possess adaptive immune systems based on a vast, somatically diversified repertoire of lymphocyte-bound antigen receptors. Despite these similarities to antibody and T cell receptors (TCR) of later vertebrates, the variable lymphocyte receptors (VLR) are not related to the immunoglobulin (Ig)-superfamily of genes; and instead of V(D)J recombination VLR are somatically assembled by a gene conversion process. However, recent studies have revealed two lamprey lymphocyte subsets so closely resembling B cells and T cells that separate lymphocyte lineages must have already existed in the ancestral vertebrate, before Ig/TCR emergence. VLR and Ig/TCR arose independently, but the convergent evolution they display actually reflects their selection in cells with specialized functions.
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Affiliation(s)
- Ellen Hsu
- Department of Physiology and Pharmacology, State University of New York and Health Science Center at Brooklyn, Brooklyn, NY 11203, USA.
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44
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Abstract
The zebrafish is an excellent model system to study vertebrate blood cell development due to a highly conserved hematopoietic system, optical transparency, and amenability to both forward and reverse genetic approaches. The development of functional assays to analyze the biology of hematopoietic mutants and diseased animals remains a work in progress. Here we discuss recent advances in zebrafish hematology, prospective isolation techniques, cellular transplantation, and culture-based assays that now provide more rigorous tests of hematopoietic stem and progenitor cell function. Together with the proven strengths of the zebrafish, the development and refinement of these assays further enable efforts to better understand the development and evolution of the vertebrate hematopoietic system.
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Affiliation(s)
- David L Stachura
- Division of Biological Sciences, Section of Cell and Developmental Biology, University of California San Diego, La Jolla, California, USA
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45
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Zhu C, Hsu E. Error-prone DNA repair activity during somatic hypermutation in shark B lymphocytes. THE JOURNAL OF IMMUNOLOGY 2010; 185:5336-47. [PMID: 20921520 DOI: 10.4049/jimmunol.1000779] [Citation(s) in RCA: 20] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 01/08/2023]
Abstract
Sharks are representatives of the earliest vertebrates that possess an immune system utilizing V(D)J recombination to generate Ag receptors. Their Ab repertoire diversity is based in part on a somatic hypermutation process that introduces adjacent nucleotide substitutions of 2-5 bp. We have isolated mutant nonfunctional Ig rearrangements and intronic flank sequences to characterize the nonselected, intrinsic properties of this phenomenon; changes unique to shark were observed. Duplications and deletions were associated with N additions, suggesting participation of a DNA polymerase with some degree of template independence during the repair of DNA breaks initiated by activation-induced cytidine deaminase. Other mutations were consistent with some in vitro activities of mammalian translesion DNA polymerase η: tandem base substitutions, strand slippage, and small insertions/deletions. The nature of substitution patterns shows that DNA lesions at shark Ig genes recruit DNA repair factors with a species-specific repertoire of activities. We speculate that the tandem mutations are introduced by direct sequential misinsertions and that, in shark B cells, the mispairs tend to be extended rather than proofread. Despite extensive changes undergone by some mutants, the physical range of mutational activity remained restricted to VDJ and within the first 2-kb portion of the 6.8-kb J-C intron, perhaps a self-regulating aspect of activation-induced cytidine deaminase action that is conserved in evolution.
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Affiliation(s)
- Catherine Zhu
- Department of Physiology and Pharmacology, State University of New York, Health Science Center at Brooklyn, Brooklyn, NY 11203-2098, USA
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46
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Koppang EO, Fischer U, Moore L, Tranulis MA, Dijkstra JM, Köllner B, Aune L, Jirillo E, Hordvik I. Salmonid T cells assemble in the thymus, spleen and in novel interbranchial lymphoid tissue. J Anat 2010; 217:728-39. [PMID: 20880086 DOI: 10.1111/j.1469-7580.2010.01305.x] [Citation(s) in RCA: 133] [Impact Index Per Article: 8.9] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/19/2022] Open
Abstract
In modern bony fishes, or teleost fish, the general lack of leucocyte markers has greatly hampered investigations of the anatomy of the immune system and its reactions involved in inflammatory responses. We have previously reported the cloning and sequencing of the salmon CD3 complex, molecules that are specifically expressed in T cells. Here, we generate and validate sera recognizing a peptide sequence of the CD3ε chain. Flow cytometry analysis revealed high numbers of CD3ε(+) or T cells in the thymus, gill and intestine, whereas lower numbers were detected in the head kidney, spleen and peripheral blood leucocytes. Subsequent morphological analysis showed accumulations of T cells in the thymus and spleen and in the newly discovered gill-located interbranchial lymphoid tissue. In the latter, the T cells are embedded in a meshwork of epithelial cells and in the spleen, they cluster in the white pulp surrounding ellipsoids. The anatomical organization of the salmonid thymic cortex and medulla seems to be composed of three layers consisting of a sub-epithelial medulla-like zone, an intermediate cortex-like zone and finally another cortex-like basal zone. Our study in the salmonid thymus reports a previously non-described tissue organization. In the intestinal tract, abundant T cells were found embedded in the epithelium. In non-lymphoid organs, the presence of T cells was limited. The results show that the interbranchial lymphoid tissue is quantitatively a very important site of T cell aggregation, strategically located to facilitate antigen encounter. The interbranchial lymphoid tissue has no resemblance to previously described lymphoid tissues.
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Affiliation(s)
- Erling O Koppang
- Section of Anatomy and Pathology, Institute of Basic Sciences and Aquatic Medicine, Norwegian School of Veterinary Science, Oslo, Norway.
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47
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Zhang YA, Salinas I, Li J, Parra D, Bjork S, Xu Z, LaPatra SE, Bartholomew J, Sunyer JO. IgT, a primitive immunoglobulin class specialized in mucosal immunity. Nat Immunol 2010; 11:827-35. [PMID: 20676094 PMCID: PMC3459821 DOI: 10.1038/ni.1913] [Citation(s) in RCA: 617] [Impact Index Per Article: 41.1] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/01/2010] [Accepted: 07/02/2010] [Indexed: 12/14/2022]
Abstract
Teleost fish are the most primitive bony vertebrates that contain immunoglobulins. In contrast to mammals and birds, these species are devoid of immunoglobulin A (IgA) or a functional equivalent. This observation suggests that specialization of immunoglobulin isotypes into mucosal and systemic responses took place during tetrapod evolution. Challenging that paradigm, here we show that IgT, an immunoglobulin isotype of unknown function, acts like a mucosal antibody. We detected responses of rainbow trout IgT to an intestinal parasite only in the gut, whereas IgM responses were confined to the serum. IgT coated most intestinal bacteria. As IgT and IgA are phylogenetically distant immunoglobulins, their specialization into mucosal responses probably occurred independently by a process of convergent evolution.
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Affiliation(s)
- Yong-An Zhang
- Department of Pathobiology, School of Veterinary Medicine, University of Pennsylvania, Philadelphia, PA, USA
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48
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Abstract
Adaptive immunity is mediated through numerous genetic and cellular processes that generate favourable somatic variants of antigen-binding receptors under evolutionary selection pressure by pathogens and other factors. Advances in our understanding of immunity in mammals and other model organisms are revealing the underlying basis and complexity of this remarkable system. Although the evolution of adaptive immunity has been thought to occur by the acquisition of novel molecular capabilities, an increasing amount of information from new model systems suggest that co-option and redirection of pre-existing systems are the main source of innovation. We combine evidence from a wide range of organisms to obtain an integrated view of the origins and patterns of divergence in adaptive immunity.
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Affiliation(s)
- Gary W Litman
- Department of Molecular Genetics, All Children's Hospital, St. Petersburg, Florida 33701, USA.
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Criscitiello MF, Ohta Y, Saltis M, McKinney EC, Flajnik MF. Evolutionarily conserved TCR binding sites, identification of T cells in primary lymphoid tissues, and surprising trans-rearrangements in nurse shark. JOURNAL OF IMMUNOLOGY (BALTIMORE, MD. : 1950) 2010; 184:6950-60. [PMID: 20488795 PMCID: PMC3222143 DOI: 10.4049/jimmunol.0902774] [Citation(s) in RCA: 68] [Impact Index Per Article: 4.5] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Subscribe] [Scholar Register] [Indexed: 11/19/2022]
Abstract
Cartilaginous fish are the oldest animals that generate RAG-based Ag receptor diversity. We have analyzed the genes and expressed transcripts of the four TCR chains for the first time in a cartilaginous fish, the nurse shark (Ginglymostoma cirratum). Northern blotting found TCR mRNA expression predominantly in lymphoid and mucosal tissues. Southern blotting suggested translocon-type loci encoding all four chains. Based on diversity of V and J segments, the expressed combinatorial diversity for gamma is similar to that of human, alpha and beta may be slightly lower, and delta diversity is the highest of any organism studied to date. Nurse shark TCRdelta have long CDR3 loops compared with the other three chains, creating binding site topologies comparable to those of mammalian TCR in basic paratope structure; additionally, nurse shark TCRdelta CDR3 are more similar to IgH CDR3 in length and heterogeneity than to other TCR chains. Most interestingly, several cDNAs were isolated that contained IgM or IgW V segments rearranged to other gene segments of TCRdelta and alpha. Finally, in situ hybridization experiments demonstrate a conservation of both alpha/beta and gamma/delta T cell localization in the thymus across 450 million years of vertebrate evolution, with gamma/delta TCR expression especially high in the subcapsular region. Collectively, these data make the first cellular identification of TCR-expressing lymphocytes in a cartilaginous fish.
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MESH Headings
- Amino Acid Sequence
- Animals
- Blotting, Northern
- Blotting, Southern
- Conserved Sequence
- Gene Expression
- Gene Expression Profiling
- Gene Rearrangement, alpha-Chain T-Cell Antigen Receptor/genetics
- Gene Rearrangement, alpha-Chain T-Cell Antigen Receptor/immunology
- Gene Rearrangement, delta-Chain T-Cell Antigen Receptor/genetics
- Gene Rearrangement, delta-Chain T-Cell Antigen Receptor/immunology
- Humans
- In Situ Hybridization
- Lymphoid Tissue/immunology
- Molecular Sequence Data
- Phylogeny
- Receptors, Antigen, T-Cell/genetics
- Receptors, Antigen, T-Cell/immunology
- Reverse Transcriptase Polymerase Chain Reaction
- Sharks/genetics
- Sharks/immunology
- T-Lymphocytes/immunology
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Affiliation(s)
- Michael F Criscitiello
- Department of Microbiology and Immunology, University of Maryland at Baltimore, Baltimore, MD 21201, USA.
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50
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Hofmann J, Greter M, Du Pasquier L, Becher B. B-cells need a proper house, whereas T-cells are happy in a cave: the dependence of lymphocytes on secondary lymphoid tissues during evolution. Trends Immunol 2010; 31:144-53. [PMID: 20181529 DOI: 10.1016/j.it.2010.01.003] [Citation(s) in RCA: 48] [Impact Index Per Article: 3.2] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/20/2009] [Revised: 01/11/2010] [Accepted: 01/14/2010] [Indexed: 12/24/2022]
Abstract
A fundamental tenet of immunology is that adaptive immune responses are initiated in secondary lymphoid tissues. This dogma has been challenged by several recent reports. We discuss how successful T cell-mediated immunity can be initiated outside of such dedicated structures, whereas they are required for adaptive humoral immunity. This resembles an ancient immune pathway in the oldest cold-blooded vertebrates, which lack lymph nodes and sophisticated B-cell responses including optimal affinity maturation. The T-cell, however, has retained the capacity to recognize antigen in a lymph node-free environment. Besides bone marrow and lung, the liver is one organ that can potentially serve as a surrogate lymphoid organ and could represent a remnant from the time before lymph nodes developed.
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Affiliation(s)
- Janin Hofmann
- Division of Neuroimmunology, Inst. Exp. Immunology, Department of Pathology, University Hospital of Zurich, 8057 Zurich, Switzerland
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