|
1
|
Durães-Oliveira J, Palma-Marques J, Moreno C, Rodrigues A, Monteiro M, Alexandre-Pires G, da Fonseca IP, Santos-Gomes G. Chagas Disease: A Silent Threat for Dogs and Humans. Int J Mol Sci 2024; 25:3840. [PMID: 38612650 PMCID: PMC11011309 DOI: 10.3390/ijms25073840] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/06/2024] [Revised: 03/15/2024] [Accepted: 03/22/2024] [Indexed: 04/14/2024] Open
Abstract
Chagas disease (CD) is a vector-borne Neglected Zoonotic Disease (NZD) caused by a flagellate protozoan, Trypanosoma cruzi, that affects various mammalian species across America, including humans and domestic animals. However, due to an increase in population movements and new routes of transmission, T. cruzi infection is presently considered a worldwide health concern, no longer restricted to endemic countries. Dogs play a major role in the domestic cycle by acting very efficiently as reservoirs and allowing the perpetuation of parasite transmission in endemic areas. Despite the significant progress made in recent years, still there is no vaccine against human and animal disease, there are few drugs available for the treatment of human CD, and there is no standard protocol for the treatment of canine CD. In this review, we highlight human and canine Chagas Disease in its different dimensions and interconnections. Dogs, which are considered to be the most important peridomestic reservoir and sentinel for the transmission of T. cruzi infection in a community, develop CD that is clinically similar to human CD. Therefore, an integrative approach, based on the One Health concept, bringing together the advances in genomics, immunology, and epidemiology can lead to the effective development of vaccines, new treatments, and innovative control strategies to tackle CD.
Collapse
Affiliation(s)
- João Durães-Oliveira
- Global Health and Tropical Medicine, GHTM, Associate Laboratory in Translation and Innovation Towards Global Health, LA-REAL, Instituto de Higiene e Medicina Tropical, IHMT, Universidade NOVA de Lisboa, UNL, Rua da Junqueira 100, 1349-008 Lisbon, Portugal; (J.D.-O.); (G.S.-G.)
| | - Joana Palma-Marques
- Global Health and Tropical Medicine, GHTM, Associate Laboratory in Translation and Innovation Towards Global Health, LA-REAL, Instituto de Higiene e Medicina Tropical, IHMT, Universidade NOVA de Lisboa, UNL, Rua da Junqueira 100, 1349-008 Lisbon, Portugal; (J.D.-O.); (G.S.-G.)
| | - Cláudia Moreno
- Global Health and Tropical Medicine, GHTM, Associate Laboratory in Translation and Innovation Towards Global Health, LA-REAL, Instituto de Higiene e Medicina Tropical, IHMT, Universidade NOVA de Lisboa, UNL, Rua da Junqueira 100, 1349-008 Lisbon, Portugal; (J.D.-O.); (G.S.-G.)
| | - Armanda Rodrigues
- Global Health and Tropical Medicine, GHTM, Associate Laboratory in Translation and Innovation Towards Global Health, LA-REAL, Instituto de Higiene e Medicina Tropical, IHMT, Universidade NOVA de Lisboa, UNL, Rua da Junqueira 100, 1349-008 Lisbon, Portugal; (J.D.-O.); (G.S.-G.)
| | - Marta Monteiro
- Global Health and Tropical Medicine, GHTM, Associate Laboratory in Translation and Innovation Towards Global Health, LA-REAL, Instituto de Higiene e Medicina Tropical, IHMT, Universidade NOVA de Lisboa, UNL, Rua da Junqueira 100, 1349-008 Lisbon, Portugal; (J.D.-O.); (G.S.-G.)
- Centre for Interdisciplinary Research in Animal Health, CIISA, Faculty of Veterinary Medicine, FMV, University of Lisbon, ULisboa, 1649-004 Lisbon, Portugal; (G.A.-P.); (I.P.d.F.)
- Associate Laboratory for Animal and Veterinary Sciences (AL4AnimalS), 1300-477 Lisbon, Portugal
| | - Graça Alexandre-Pires
- Centre for Interdisciplinary Research in Animal Health, CIISA, Faculty of Veterinary Medicine, FMV, University of Lisbon, ULisboa, 1649-004 Lisbon, Portugal; (G.A.-P.); (I.P.d.F.)
- Associate Laboratory for Animal and Veterinary Sciences (AL4AnimalS), 1300-477 Lisbon, Portugal
| | - Isabel Pereira da Fonseca
- Centre for Interdisciplinary Research in Animal Health, CIISA, Faculty of Veterinary Medicine, FMV, University of Lisbon, ULisboa, 1649-004 Lisbon, Portugal; (G.A.-P.); (I.P.d.F.)
- Associate Laboratory for Animal and Veterinary Sciences (AL4AnimalS), 1300-477 Lisbon, Portugal
| | - Gabriela Santos-Gomes
- Global Health and Tropical Medicine, GHTM, Associate Laboratory in Translation and Innovation Towards Global Health, LA-REAL, Instituto de Higiene e Medicina Tropical, IHMT, Universidade NOVA de Lisboa, UNL, Rua da Junqueira 100, 1349-008 Lisbon, Portugal; (J.D.-O.); (G.S.-G.)
| |
Collapse
|
|
2
|
Cellular Stress and Senescence Induction during Trypanosoma cruzi Infection. Trop Med Infect Dis 2022; 7:tropicalmed7070129. [PMID: 35878141 PMCID: PMC9323233 DOI: 10.3390/tropicalmed7070129] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/10/2022] [Revised: 07/05/2022] [Accepted: 07/07/2022] [Indexed: 11/17/2022] Open
Abstract
Chagas disease (CD) is a neglected tropical disease caused by Trypanosoma cruzi infection that, despite being discovered over a century ago, remains a public health problem, mainly in developing countries. Since T. cruzi can infect a wide range of mammalian host cells, parasite–host interactions may be critical to infection outcome. The intense immune stimulation that helps the control of the parasite’s replication and dissemination may also be linked with the pathogenesis and symptomatology worsening. Here, we discuss the findings that support the notion that excessive immune system stimulation driven by parasite persistence might elicit a progressive loss and collapse of immune functions. In this context, cellular stress and inflammatory responses elicited by T. cruzi induce fibroblast and other immune cell senescence phenotypes that may compromise the host’s capacity to control the magnitude of T. cruzi-induced inflammation, contributing to parasite persistence and CD progression. A better understanding of the steps involved in the induction of this chronic inflammatory status, which disables host defense capacity, providing an extra advantage to the parasite and predisposing infected hosts prematurely to immunosenescence, may provide insights to designing and developing novel therapeutic approaches to prevent and treat Chagas disease.
Collapse
|
|
3
|
Nihei J, Cardillo F, Mengel J. The Blockade of Interleukin-2 During the Acute Phase of Trypanosoma cruzi Infection Reveals Its Dominant Regulatory Role. Front Cell Infect Microbiol 2021; 11:758273. [PMID: 34869064 PMCID: PMC8635756 DOI: 10.3389/fcimb.2021.758273] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/13/2021] [Accepted: 10/29/2021] [Indexed: 11/16/2022] Open
Abstract
Trypanosoma cruzi infection causes Chagas’ disease in humans. The infection activates the innate and adaptative immunity in an orchestrated immune response to control parasite growth, guaranteeing host survival. Despite an effective immune response to the parasite in the acute phase, the infection progresses to a chronic stage. The parasite infects different tissues such as peripheral neurons, the brain, skeletal muscle, and heart muscle, among many others. It is evident now that tissue-specific immune responses may develop along with anti-parasite immunity. Therefore, mechanisms to regulate immunity and to ensure tissue-specific tolerance are operating during the infection. Studying those immunoregulatory mechanisms is fundamental to improve host protection or control inflammatory reactions that may lead to pathology. The role of IL-2 during T. cruzi infection is not established. IL-2 production by T cells is strongly down-modulated early in the disease by unknown mechanisms and remains low during the chronic phase of the disease. IL-2 activates NK cells, CD4, and CD8 T cells and may be necessary to immunity development. Also, the expansion and maintenance of regulatory T cells require IL-2. Thus, IL-2 may be a key cytokine involved in promoting or down-regulating immune responses, probably in a dose-dependent manner. This study blocked IL-2 during the acute T. cruzi infection by using a neutralizing monoclonal antibody. The results show that parasitemia and mortality rate was lower in animals treated with anti-IL-2. The percentages and total numbers of CD4+CD25+Foxp3+ T cells diminished within three weeks of infection. The numbers of splenic activated/memory CD4 and CD8 splenic T cells increased during the acute infection. T cells producing IFN-γ, TNF-α and IL-10 also augmented in anti-IL-2-treated infected mice. The IL-2 blockade also increased the numbers of inflammatory cells in the heart and skeletal muscles and the amount of IL-17 produced by heart T cells. These results suggest that IL-2 might be involved in the immune regulatory response during the acute T. cruzi infection, dampening T cell activation through the expansion/maintenance of regulatory T cells and regulating IL-17 production. Therefore, the IL-2 pathway is an attractive target for therapeutic purposes in acute and chronic phases of Chagas’ disease.
Collapse
Affiliation(s)
- Jorge Nihei
- Gonçalo Moniz Research Institute, Oswaldo Cruz Foundation (Fiocruz), Salvador, Brazil.,Center of Health Sciences, Federal University of Recôncavo da Bahia (UFRP), Santo Antonio de Jesus, Brazil
| | - Fabiola Cardillo
- Gonçalo Moniz Research Institute, Oswaldo Cruz Foundation (Fiocruz), Salvador, Brazil
| | - Jose Mengel
- Oswaldo Cruz Institute, Oswaldo Cruz Foundation (Fiocruz), Rio de Janeiro, Brazil.,Petropolis Medical School, University Faculties Arthur Sa Earp Neto (FMP/UNIFASE), Petropolis, Brazil
| |
Collapse
|
|
4
|
García LN, Leimgruber C, Nicola JP, Quintar AA, Maldonado CA. Neonatal endotoxin stimulation is associated with a long-term bronchiolar epithelial expression of innate immune and anti-allergic markers that attenuates the allergic response. PLoS One 2020; 15:e0226233. [PMID: 32379832 PMCID: PMC7205282 DOI: 10.1371/journal.pone.0226233] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/11/2019] [Accepted: 04/22/2020] [Indexed: 11/19/2022] Open
Abstract
Allergic asthma is the most common phenotype of the pathology, having an early-onset in childhood and producing a Th2-driven airways remodeling process that leads to symptoms and pathophysiological changes. The avoidance of aeroallergen exposure in early life has been shown to prevent asthma, but without repeated success and with the underlying preventive mechanisms at the beginning of asthma far to be fully recognized. In the present study, we aimed to evaluate if neonatal LPS-induced boost in epithelial host defenses contribute to prevent OVA-induced asthma in adult mice. To this, we focused on the response of bronchiolar club cells (CC), which are highly specialized in maintaining the epithelial homeostasis in the lung. In these cells, neonatal LPS administration increased the expression of TLR4 and TNFα, as well as the immunodulatory/antiallergic proteins: club cell secretory protein (CCSP) and surfactant protein D (SP-D). LPS also prevented mucous metaplasia of club cells and reduced the epidermal growth factor receptor (EGFR)-dependent mucin overproduction, with mice displaying normal breathing patterns after OVA challenge. Furthermore, the overexpression of the epithelial Th2-related molecule TSLP was blunted, and normal TSLP and IL-4 levels were found in the bronchoalveolar lavage. A lower eosinophilia was detected in LPS-pretreated mice, along with an increase in phagocytes and regulatory cells (CD4+CD25+FOXP3+ and CD4+IL-10+), together with higher levels of IL-12 and TNFα. In conclusion, our study demonstrates stable asthma-preventive epithelial effects promoted by neonatal LPS stimulation, leading to the presence of regulatory cells in the lung. These anti-allergic dynamic mechanisms would be overlaid in the epithelium, favored by an adequate epidemiological environment, during the development of asthma.
Collapse
Affiliation(s)
- Luciana Noemi García
- Centro de Microscopía Electrónica, Universidad Nacional de Córdoba, Facultad de Ciencias Médicas, Córdoba, Argentina
- Consejo Nacional de Investigaciones Científicas y Técnicas (CONICET), Instituto de Investigaciones en Ciencias de la Salud (INICSA), Córdoba, Argentina
| | - Carolina Leimgruber
- Consejo Nacional de Investigaciones Científicas y Técnicas (CONICET), Instituto de Investigaciones en Ciencias de la Salud (INICSA), Córdoba, Argentina
| | - Juan Pablo Nicola
- Departamento de Bioquímica Clínica, Universidad Nacional de Córdoba, Facultad de Ciencias Químicas, Córdoba, Argentina
- Consejo Nacional de Investigaciones Científicas y Técnicas (CONICET), Centro de Investigaciones en Bioquímica Clínica e Inmunología (CIBICI), Córdoba, Argentina
| | - Amado Alfredo Quintar
- Centro de Microscopía Electrónica, Universidad Nacional de Córdoba, Facultad de Ciencias Médicas, Córdoba, Argentina
- Consejo Nacional de Investigaciones Científicas y Técnicas (CONICET), Instituto de Investigaciones en Ciencias de la Salud (INICSA), Córdoba, Argentina
| | - Cristina Alicia Maldonado
- Centro de Microscopía Electrónica, Universidad Nacional de Córdoba, Facultad de Ciencias Médicas, Córdoba, Argentina
- Consejo Nacional de Investigaciones Científicas y Técnicas (CONICET), Instituto de Investigaciones en Ciencias de la Salud (INICSA), Córdoba, Argentina
| |
Collapse
|
|
5
|
Interleukin-18 in Health and Disease. Int J Mol Sci 2019; 20:ijms20030649. [PMID: 30717382 PMCID: PMC6387150 DOI: 10.3390/ijms20030649] [Citation(s) in RCA: 357] [Impact Index Per Article: 59.5] [Reference Citation Analysis] [Abstract] [Key Words] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/21/2018] [Revised: 01/28/2019] [Accepted: 01/29/2019] [Indexed: 12/12/2022] Open
Abstract
Interleukin (IL)-18 was originally discovered as a factor that enhanced IFN-γ production from anti-CD3-stimulated Th1 cells, especially in the presence of IL-12. Upon stimulation with Ag plus IL-12, naïve T cells develop into IL-18 receptor (IL-18R) expressing Th1 cells, which increase IFN-γ production in response to IL-18 stimulation. Therefore, IL-12 is a commitment factor that induces the development of Th1 cells. In contrast, IL-18 is a proinflammatory cytokine that facilitates type 1 responses. However, IL-18 without IL-12 but with IL-2, stimulates NK cells, CD4+ NKT cells, and established Th1 cells, to produce IL-3, IL-9, and IL-13. Furthermore, together with IL-3, IL-18 stimulates mast cells and basophils to produce IL-4, IL-13, and chemical mediators such as histamine. Therefore, IL-18 is a cytokine that stimulates various cell types and has pleiotropic functions. IL-18 is a member of the IL-1 family of cytokines. IL-18 demonstrates a unique function by binding to a specific receptor expressed on various types of cells. In this review article, we will focus on the unique features of IL-18 in health and disease in experimental animals and humans.
Collapse
|
|
6
|
VEGA-ROYERO S, SIBONA GJ, CASTAÑO S, CONDAT CA. MODELING PARASITE REDUCTION MECHANISMS IN CHAGAS DISEASE. J BIOL SYST 2015. [DOI: 10.1142/s021833901540001x] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/18/2022]
Abstract
Various procedures have been proposed to reduce parasitemia during Chagas disease. Here we analyze in detail models developed to predict the possible outcomes of two of these treatments. The model solutions reproduce available experimental population data and can be used as tools to help researchers to find a cure or, at least, an optimal treatment to reduce cardiac cell damage. In particular, we study how the phase diagram describing the infection outcome is modified by the application of the ganglioside GM1, finding the optimum concentration of the drug in terms of the parameters characterizing its influence on the parasite-host interaction. We also investigate the use of the non-pathogenic parasite T. rangeli to reduce T. cruzi load in a mixed infection, finding that this method is not effective against all T. cruzi strains. Furthermore, we compare phase portraits of the evolution of the disease for a single and a mixed infection, and evaluate the cell damage as a function of the time elapsed between both infections, remarking on the temporary protective effect of the reaction to T. rangeli.
Collapse
Affiliation(s)
- S. VEGA-ROYERO
- IFEG-CONICET and FaMAF, Universidad Nacional de Córdoba, Ciudad Universitaria, 5000-Córdoba, Argentina
| | - G. J. SIBONA
- IFEG-CONICET and FaMAF, Universidad Nacional de Córdoba, Ciudad Universitaria, 5000-Córdoba, Argentina
| | - S. CASTAÑO
- IFEG-CONICET and FaMAF, Universidad Nacional de Córdoba, Ciudad Universitaria, 5000-Córdoba, Argentina
| | - C. A. CONDAT
- IFEG-CONICET and FaMAF, Universidad Nacional de Córdoba, Ciudad Universitaria, 5000-Córdoba, Argentina
| |
Collapse
|
|
7
|
Brima W, Eden DJ, Mehdi SF, Bravo M, Wiese MM, Stein J, Almonte V, Zhao D, Kurland I, Pessin JE, Zima T, Tanowitz HB, Weiss LM, Roth J, Nagajyothi F. The brighter (and evolutionarily older) face of the metabolic syndrome: evidence from Trypanosoma cruzi infection in CD-1 mice. Diabetes Metab Res Rev 2015; 31:346-359. [PMID: 25613819 PMCID: PMC4427523 DOI: 10.1002/dmrr.2636] [Citation(s) in RCA: 29] [Impact Index Per Article: 2.9] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/09/2014] [Accepted: 12/21/2014] [Indexed: 01/13/2023]
Abstract
BACKGROUND Infection with Trypanosoma cruzi, the protozoan parasite that causes Chagas disease, results in chronic infection that leads to cardiomyopathy with increased mortality and morbidity in endemic regions. In a companion study, our group found that a high-fat diet (HFD) protected mice from T. cruzi-induced myocardial damage and significantly reduced post-infection mortality during acute T. cruzi infection. METHODS In the present study metabolic syndrome was induced prior to T. cruzi infection by feeding a high fat diet. Also, mice were treated with anti-diabetic drug metformin. RESULTS In the present study, the lethality of T. cruzi (Brazil strain) infection in CD-1 mice was reduced from 55% to 20% by an 8-week pre-feeding of an HFD to induce obesity and metabolic syndrome. The addition of metformin reduced mortality to 3%. CONCLUSIONS It is an interesting observation that both the high fat diet and the metformin, which are known to differentially attenuate host metabolism, effectively modified mortality in T. cruzi-infected mice. In humans, the metabolic syndrome, as presently construed, produces immune activation and metabolic alterations that promote complications of obesity and diseases of later life, such as myocardial infarction, stroke, diabetes, Alzheimer's disease and cancer. Using an evolutionary approach, we hypothesized that for millions of years, the channeling of host resources into immune defences starting early in life ameliorated the effects of infectious diseases, especially chronic infections, such as tuberculosis and Chagas disease. In economically developed countries in recent times, with control of the common devastating infections, epidemic obesity and lengthening of lifespan, the dwindling benefits of the immune activation in the first half of life have been overshadowed by the explosion of the syndrome's negative effects in later life.
Collapse
Affiliation(s)
- Wunnie Brima
- Laboratory of Diabetes and Diabetes-Related Research, Feinstein Institute for Medical Research, North Shore-Long Island Jewish Health System, Manhasset, NY
- Department of Medicine, Albert Einstein College of Medicine, Bronx, NY
- James J Peters VA Medical Center, Mount Sinai Medical Center Health System, Bronx, NY
- Charles University, Prague, Czech Republic
| | - Daniel J. Eden
- Laboratory of Diabetes and Diabetes-Related Research, Feinstein Institute for Medical Research, North Shore-Long Island Jewish Health System, Manhasset, NY
| | - Syed Faizan Mehdi
- Laboratory of Diabetes and Diabetes-Related Research, Feinstein Institute for Medical Research, North Shore-Long Island Jewish Health System, Manhasset, NY
| | - Michelle Bravo
- Laboratory of Diabetes and Diabetes-Related Research, Feinstein Institute for Medical Research, North Shore-Long Island Jewish Health System, Manhasset, NY
| | - Mohammad M. Wiese
- Laboratory of Diabetes and Diabetes-Related Research, Feinstein Institute for Medical Research, North Shore-Long Island Jewish Health System, Manhasset, NY
| | - Joanna Stein
- Laboratory of Diabetes and Diabetes-Related Research, Feinstein Institute for Medical Research, North Shore-Long Island Jewish Health System, Manhasset, NY
| | - Vanessa Almonte
- Department of Medicine, Albert Einstein College of Medicine, Bronx, NY
| | - Dazhi Zhao
- Department of Medicine, Albert Einstein College of Medicine, Bronx, NY
| | - Irwin Kurland
- Department of Medicine, Albert Einstein College of Medicine, Bronx, NY
| | - Jeffrey E. Pessin
- Department of Medicine, Albert Einstein College of Medicine, Bronx, NY
| | - Tomas Zima
- Charles University, Prague, Czech Republic
| | | | - Louis M. Weiss
- Department of Medicine, Albert Einstein College of Medicine, Bronx, NY
| | - Jesse Roth
- Laboratory of Diabetes and Diabetes-Related Research, Feinstein Institute for Medical Research, North Shore-Long Island Jewish Health System, Manhasset, NY
- Department of Medicine, Albert Einstein College of Medicine, Bronx, NY
- Hofstra North Shore-LIJ School of Medicine, North Shore-Long Island Jewish Health System, Hempstead, NY
| | - Fnu Nagajyothi
- Department of Medicine, Albert Einstein College of Medicine, Bronx, NY
| |
Collapse
|
|
8
|
Aparicio-Burgos JE, Zepeda-Escobar JA, de Oca-Jimenez RM, Estrada-Franco JG, Barbabosa-Pliego A, Ochoa-García L, Alejandre-Aguilar R, Rivas N, Peñuelas-Rivas G, Val-Arreola M, Gupta S, Salazar-García F, Garg NJ, Vázquez-Chagoyán JC. Immune protection against Trypanosoma cruzi induced by TcVac4 in a canine model. PLoS Negl Trop Dis 2015; 9:e0003625. [PMID: 25853654 PMCID: PMC4390229 DOI: 10.1371/journal.pntd.0003625] [Citation(s) in RCA: 28] [Impact Index Per Article: 2.8] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/01/2014] [Accepted: 02/16/2015] [Indexed: 12/02/2022] Open
Abstract
Chagas disease, caused by Trypanosoma cruzi, is endemic in southern parts of the American continent. Herein, we have tested the protective efficacy of a DNA-prime/T. rangeli-boost (TcVac4) vaccine in a dog (Canis familiaris) model. Dogs were immunized with two-doses of DNA vaccine (pcDNA3.1 encoding TcG1, TcG2, and TcG4 antigens plus IL-12- and GM-CSF-encoding plasmids) followed by two doses of glutaraldehyde-inactivated T. rangeli epimastigotes (TrIE); and challenged with highly pathogenic T. cruzi (SylvioX10/4) isolate. Dogs given TrIE or empty pcDNA3.1 were used as controls. We monitored post-vaccination and post-challenge infection antibody response by an ELISA, parasitemia by blood analysis and xenodiagnosis, and heart function by electrocardiography. Post-mortem anatomic and pathologic evaluation of the heart was conducted. TcVac4 induced a strong IgG response (IgG2>IgG1) that was significantly expanded post-infection, and moved to a nearly balanced IgG2/IgG1 response in chronic phase. In comparison, dogs given TrIE or empty plasmid DNA only developed high IgG titers with IgG2 predominance in response to T. cruzi infection. Blood parasitemia, tissue parasite foci, parasite transmission to triatomines, electrocardiographic abnormalities were significantly lower in TcVac4-vaccinated dogs than was observed in dogs given TrIE or empty plasmid DNA only. Macroscopic and microscopic alterations, the hallmarks of chronic Chagas disease, were significantly decreased in the myocardium of TcVac4-vaccinated dogs. We conclude that TcVac4 induced immunity was beneficial in providing resistance to T. cruzi infection, evidenced by control of chronic pathology of the heart and preservation of cardiac function in dogs. Additionally, TcVac4 vaccination decreased the transmission of parasites from vaccinated/infected animals to triatomines.
Collapse
Affiliation(s)
| | - José A. Zepeda-Escobar
- Centro de Investigación y Estudios Avanzados en Salud Animal, Universidad Autónoma de Estado de México, Toluca, México
| | - Roberto Montes de Oca-Jimenez
- Centro de Investigación y Estudios Avanzados en Salud Animal, Universidad Autónoma de Estado de México, Toluca, México
| | - José G. Estrada-Franco
- Centro de Investigación y Estudios Avanzados en Salud Animal, Universidad Autónoma de Estado de México, Toluca, México
| | - Alberto Barbabosa-Pliego
- Centro de Investigación y Estudios Avanzados en Salud Animal, Universidad Autónoma de Estado de México, Toluca, México
| | - Laucel Ochoa-García
- Laboratorio Estatal de Salud Pública del Instituto Salud del Estado de México, Toluca, México
| | - Ricardo Alejandre-Aguilar
- Laboratorio de Entomología, Departamento de Parasitología, Escuela Nacional de Ciencias Biológicas del Instituto Politécnico Nacional, México City, México
| | - Nancy Rivas
- Laboratorio de Entomología, Departamento de Parasitología, Escuela Nacional de Ciencias Biológicas del Instituto Politécnico Nacional, México City, México
| | - Giovanna Peñuelas-Rivas
- Centro de Investigación y Estudios Avanzados en Salud Animal, Universidad Autónoma de Estado de México, Toluca, México
| | - Margarita Val-Arreola
- Hospital General de Zona No. 2, Instituto Mexicano del Seguro Social, Irapuato, México
| | - Shivali Gupta
- Department of Microbiology and Immunology, University of Texas Medical Branch (UTMB), Galveston, Texas, United States of America
| | - Felix Salazar-García
- Centro de Investigación y Estudios Avanzados en Salud Animal, Universidad Autónoma de Estado de México, Toluca, México
| | - Nisha J. Garg
- Department of Microbiology and Immunology, University of Texas Medical Branch (UTMB), Galveston, Texas, United States of America
- Department of Pathology, and Faculty of the Institute for Human Infection and Immunity, and the Sealy Center for Vaccine Development, University of Texas Medical Branch (UTMB), Galveston, Texas, United States of America
| | - Juan C. Vázquez-Chagoyán
- Centro de Investigación y Estudios Avanzados en Salud Animal, Universidad Autónoma de Estado de México, Toluca, México
| |
Collapse
|
|
9
|
Basso B, Marini V. Experimental Chagas disease in Balb/c mice previously vaccinated with T. rangeli. II. The innate immune response shows immunological memory: reality or fiction? Immunobiology 2014; 220:428-36. [PMID: 25454810 DOI: 10.1016/j.imbio.2014.10.003] [Citation(s) in RCA: 5] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/23/2014] [Revised: 10/01/2014] [Accepted: 10/12/2014] [Indexed: 11/30/2022]
Abstract
Trypanosoma cruzi is a real challenge to the host's immune system, because it requires strong humoral and cellular immune response to remove circulating trypomastigote forms, and to prevent the replication of amastigote forms in tissues, involving many regulator and effector components. This protozoan is responsible for Chagas disease, a major public health problem in Latinamerica. We have developed a model of vaccination with Trypanosoma rangeli, a parasite closely related to T. cruzi, but nonpathogenic to humans, which reduces the infectiousness in three different species of animals, mice, dogs and guinea pigs, against challenge with T. cruzi. In a previous work, we demonstrated that mice vaccinated with T. rangeli showed important soluble mediators that stimulate phagocytic activity versus only infected groups. The aim of this work was to study the innate immune response in mice vaccinated or not with T. rangeli. Different population cells and some soluble mediators (cytokines) in peritoneal fluid and plasma in mice vaccinated-infected and only infected with T. cruzi were studied. In the first hours of challenge vaccinated mice showed an increase of macrophages, NK, granulocytes, and regulation of IL6, IFNγ, TNFα and IL10, with an increase of IL12, with respect to only infected mice. Furthermore an increase was observed of Li T, Li B responsible for adaptative response. Finally the findings showed that the innate immune response plays an important role in vaccinated mice for the early elimination of the parasites, complementary with the adaptative immune response, suggesting that vaccination with T. rangeli modulates the innate response, which develops some kind of immunological memory, recognizing shared antigens with T. cruzi. These results could contribute to the knowledge of new mechanisms which would have an important role in the immune response to Chagas disease.
Collapse
Affiliation(s)
- B Basso
- Department of Paediatrics, Neonatology Service, Medicine School, National Cordoba University, Argentina; National Co-ordination of Vector Control, Argentina.
| | - V Marini
- Department of Immunology Medicine School, Catholic University of Cordoba, Argentina
| |
Collapse
|
|
10
|
Cosentino-Gomes D, Rocco-Machado N, Meyer-Fernandes JR. Rhodnius prolixus: modulation of antioxidant defenses by Trypanosoma rangeli. Exp Parasitol 2014; 145:118-24. [PMID: 25131776 DOI: 10.1016/j.exppara.2014.08.002] [Citation(s) in RCA: 7] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/09/2013] [Revised: 05/07/2014] [Accepted: 08/03/2014] [Indexed: 10/24/2022]
Abstract
Trypanosoma rangeli is a protozoan parasite of insects and mammals that is challenged by the constant action of reactive oxygen species, generated either by its own metabolism or through the host immune response. The aim of this work was to investigate whether T. rangeli is able to modify the redox state of its insect vector, Rhodnius prolixus, through the modulation of such antioxidant enzymes as superoxide dismutase (SOD), catalase, and GPx present in the midgut of the insect. We verified that in R. prolixus fed with blood infected with T. rangeli there is an increase in SOD activity in the anterior and posterior midguts. However, the activities of enzymes related to hydrogen peroxide and hydroperoxides metabolism, such as catalase and GPx, were decreased in relation to the insect control group, which was only fed blood. These changes in the redox state of the vector led to an increase in lipid peroxidation and thiol oxidation levels in the anterior and posterior midgut tissues. We also verified that the addition of 1 mM GSH in the blood meal of the infected insects increased the proliferation of these parasites by 50%. These results suggest that there is an increase in oxidative stress in the insect gut during T. rangeli infection, and this condition could contribute to the control of the proliferation of these parasites.
Collapse
Affiliation(s)
- Daniela Cosentino-Gomes
- Institute of Medical Biochemistry, Federal University of Rio de Janeiro (UFRJ), CCS, Bloco H, Cidade Universitária, Ilha do Fundão, 21941-590 Rio de Janeiro, RJ, Brazil; Institute of National Science and Technology of Structural Biology and Bioimage (INCTBEB), CCS, Bloco H, Cidade Universitária, Ilha do Fundão, 21941-590 Rio de Janeiro, RJ, Brazil
| | - Nathália Rocco-Machado
- Institute of Medical Biochemistry, Federal University of Rio de Janeiro (UFRJ), CCS, Bloco H, Cidade Universitária, Ilha do Fundão, 21941-590 Rio de Janeiro, RJ, Brazil; Institute of National Science and Technology of Structural Biology and Bioimage (INCTBEB), CCS, Bloco H, Cidade Universitária, Ilha do Fundão, 21941-590 Rio de Janeiro, RJ, Brazil.
| | - José Roberto Meyer-Fernandes
- Institute of Medical Biochemistry, Federal University of Rio de Janeiro (UFRJ), CCS, Bloco H, Cidade Universitária, Ilha do Fundão, 21941-590 Rio de Janeiro, RJ, Brazil; Institute of National Science and Technology of Structural Biology and Bioimage (INCTBEB), CCS, Bloco H, Cidade Universitária, Ilha do Fundão, 21941-590 Rio de Janeiro, RJ, Brazil.
| |
Collapse
|
|
11
|
Cazorla SI, Frank FM, Malchiodi EL. Vaccination approaches againstTrypanosoma cruziinfection. Expert Rev Vaccines 2014; 8:921-35. [DOI: 10.1586/erv.09.45] [Citation(s) in RCA: 56] [Impact Index Per Article: 5.1] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/17/2022]
|
|
12
|
Basso B, Moretti E, Fretes R. Vaccination with Trypanosoma rangeli induces resistance of guinea pigs to virulent Trypanosoma cruzi. Vet Immunol Immunopathol 2014; 157:119-23. [DOI: 10.1016/j.vetimm.2013.10.011] [Citation(s) in RCA: 12] [Impact Index Per Article: 1.1] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/10/2013] [Revised: 10/01/2013] [Accepted: 10/21/2013] [Indexed: 11/27/2022]
|
|
13
|
Can we heal Chagas infection? J Theor Biol 2014; 340:23-9. [DOI: 10.1016/j.jtbi.2013.09.002] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/13/2013] [Revised: 09/01/2013] [Accepted: 09/03/2013] [Indexed: 11/22/2022]
|
|
14
|
Basso B, Marini V. Experimental Chagas disease. Innate immune response in Balb/c mice previously vaccinated with Trypanosoma rangeli. I. The macrophage shows immunological memory: Reality or fiction? Immunobiology 2013; 219:275-84. [PMID: 24321621 DOI: 10.1016/j.imbio.2013.10.012] [Citation(s) in RCA: 8] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/20/2013] [Revised: 10/27/2013] [Accepted: 10/31/2013] [Indexed: 12/29/2022]
Abstract
Chagas' disease, caused by Trypanosoma cruzi, is a major vector borne health problem in Latin America and an emerging or re-emerging infectious disease in several countries. Immune response to T. cruzi infection is highly complex and involves many components, both regulators and effectors. Although different parasites have been shown to activate different mechanisms of innate immunity, T. cruzi is often able to survive and replicate in its host because they are well adapted to resisting host defences. An experimental model for vaccinating mice with Trypanosoma rangeli, a parasite closely related to T. cruzi, but nonpathogenic to humans, has been designed in our laboratory, showing protection against challenge with T. cruzi infection. The aim of this work was to analyze some mechanisms of the early innate immune response in T. rangeli vaccinated mice challenged with T. cruzi. For this purpose, some interactions were studied between T. cruzi and peritoneal macrophages of mice vaccinated with T. rangeli, infected or not with T. cruzi and the levels of some molecules or soluble mediators which could modify these interactions. The results in vaccinated animals showed a strong innate immune response, where the adherent cells of the vaccinated mice revealed important phagocytic activity, and some soluble mediator (Respiratory Burst: significantly increase, p ≤ 0.03; NO: the levels of vaccinated animals were lower than those of the control group; Arginasa: significantly increase, p ≤ 0.04). The results showed an important role in the early elimination of the parasites and their close relation with the absence of histological lesions that these animals present with regard to the only infected mice. This behaviour reveals that the macrophages act with some type of memory, recognizing the antigens to which they have previously been exposed, in mice were vaccinated with T. rangeli, which shares epitopes with T. cruzi.
Collapse
Affiliation(s)
- B Basso
- Department of Paediatrics, Neonatology Service, Medicine School, National Cordoba University, Argentina; National Co-ordination of Vector Control, Argentina.
| | - V Marini
- Department of Immunology Medicine School, Catholic University of Cordoba, Argentina
| |
Collapse
|
|
15
|
Sequence polymorphism in the Trypanosoma rangeli HSP70 coding genes allows typing of the parasite KP1(+) and KP1(−) groups. Exp Parasitol 2013; 133:447-53. [DOI: 10.1016/j.exppara.2013.01.001] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/08/2012] [Revised: 12/03/2012] [Accepted: 01/03/2013] [Indexed: 11/22/2022]
|
|
16
|
Basso B. Modulation of immune response in experimental Chagas disease. World J Exp Med 2013; 3:1-10. [PMID: 24520540 PMCID: PMC3905588 DOI: 10.5493/wjem.v3.i1.1] [Citation(s) in RCA: 41] [Impact Index Per Article: 3.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/10/2012] [Revised: 01/07/2013] [Accepted: 02/06/2013] [Indexed: 02/06/2023] Open
Abstract
Trypanosoma cruzi (T. cruzi), the etiological agent of Chagas disease, affects nearly 18 million people in Latin America and 90 million are at risk of infection. The parasite presents two stages of medical importance in the host, the amastigote, intracellular replicating form, and the extracellular trypomastigote, the infective form. Thus infection by T. cruzi induces a complex immune response that involves effectors and regulatory mechanisms. That is why control of the infection requires a strong humoral and cellular immune response; hence, the outcome of host-parasite interaction in the early stages of infection is extremely important. A critical event during this period of the infection is innate immune response, in which the macrophage’s role is vital. Thus, after being phagocytized, the parasite is able to develop intracellularly; however, during later periods, these cells induce its elimination by means of toxic metabolites. In turn, as the infection progresses, adaptive immune response mechanisms are triggered through the TH1 and TH2 responses. Finally, T. cruzi, like other protozoa such as Leishmania and Toxoplasma, have numerous evasive mechanisms to the immune response that make it possible to spread around the host. In our Laboratory we have developed a vaccination model in mice with Trypanosoma rangeli, nonpathogenic to humans, which modulates the immune response to infection by T. cruzi, thus protecting them. Vaccinated animals showed an important innate response (modulation of NO and other metabolites, cytokines, activation of macrophages), a strong adaptive cellular response and significant increase in specific antibodies. The modulation caused early elimination of the parasites, low parasitaemia, the absence of histological lesions and high survival rates. Even though progress has been made in the knowledge of some of these mechanisms, new studies must be conducted which could target further prophylactic and therapeutic trials against T. cruzi infection.
Collapse
|
|
17
|
Quijano-Hernandez I, Dumonteil E. Advances and challenges towards a vaccine against Chagas disease. HUMAN VACCINES 2011; 7:1184-91. [PMID: 22048121 DOI: 10.4161/hv.7.11.17016] [Citation(s) in RCA: 68] [Impact Index Per Article: 4.9] [Reference Citation Analysis] [Abstract] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 01/10/2023]
Abstract
Chagas disease is major public health problem, affecting nearly 10 million people, characterized by cardiac alterations leading to congestive heart failure and death of 20-40% of the patients infected with Trypanosoma cruzi, the protozoan parasite responsible for the disease. A vaccine would be key to improve disease control and we review here the recent advances and challenges of a T. cruzi vaccine. There is a growing consensus that a protective immune response requires the activation of a Th1 immune profile, with the stimulation of CD8 (+) T cells. Several vacines types, including recombinant proteins, DNA and viral vectors, as well as heterologous prime-boost combinations, have been found immunogenic and protective in mouse models, providing proof-of-concept data on the feasibility of a preventive or therapeutic vaccine to control a T. cruzi infection. However, several challenges such as better end-points, safety issues and trial design need to be addressed for further vaccine development to proceed.
Collapse
Affiliation(s)
- Israel Quijano-Hernandez
- Laboratorio de Parasitología, Centro de Investigaciones Regionales 'Dr. Hideyo Noguchi', Universidad Autónoma de Yucatán, Merida, Mexico
| | | |
Collapse
|
|
18
|
Marini V, Moretti E, Bermejo D, Basso B. Vaccination with Trypanosoma rangeli modulates the profiles of immunoglobulins and IL-6 at local and systemic levels in the early phase of Trypanosoma cruzi experimental infection. Mem Inst Oswaldo Cruz 2011; 106:32-7. [PMID: 21340352 DOI: 10.1590/s0074-02762011000100005] [Citation(s) in RCA: 12] [Impact Index Per Article: 0.9] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/05/2010] [Accepted: 12/08/2010] [Indexed: 12/17/2022] Open
Abstract
In America, there are two species of Trypanosoma that can infect humans: Trypanosoma cruzi, which is responsible for Chagas disease and Trypanosoma rangeli, which is not pathogenic. We have developed a model of vaccination in mice with T. rangeli epimastigotes that protects against T. cruzi infection. The goal of this work was to study the pattern of specific immunoglobulins in the peritoneum (the site of infection) and in the sera of mice immunized with T. rangeli before and after challenge with T. cruzi. Additionally, we studied the effects triggered by antigen-antibodies binding and the levels of key cytokines involved in the humoral response, such as IL-4, IL-5 and IL-6. The immunization triggered the production of antibodies reactive with T. cruzi in peritoneal fluid (PF) and in serum, mainly IgG1 and, to a lesser magnitude, IgG2. Only immunized mice developed specific IgG3 antibodies in their peritoneal cavities. Antibodies were able to bind to the surface of the parasites and agglutinate them. Among the cytokines studied, IL-6 was elevated in PF during early infection, with higher levels in non-immunized-infected mice. The results indicate that T. rangeli vaccination against T. cruzi infection triggers a high production of specific IgG isotypes in PF and sera before infection and modulates the levels of IL-6 in PF in the early periods of infection.
Collapse
Affiliation(s)
- Vanina Marini
- Laboratorio de la Coordinación Nacional de Control de Vectores, Córdoba, Argentina
| | | | | | | |
Collapse
|
|
19
|
Pineda V, Saldaña A, Monfante I, Santamaría A, Gottdenker N, Yabsley M, Rapoport G, Calzada J. Prevalence of trypanosome infections in dogs from Chagas disease endemic regions in Panama, Central America. Vet Parasitol 2011; 178:360-3. [DOI: 10.1016/j.vetpar.2010.12.043] [Citation(s) in RCA: 47] [Impact Index Per Article: 3.4] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/31/2010] [Revised: 12/15/2010] [Accepted: 12/22/2010] [Indexed: 10/18/2022]
|
|
20
|
Calzada JE, Pineda V, Garisto JD, Samudio F, Santamaria AM, Saldaña A. Human trypanosomiasis in the eastern region of the Panama Province: new endemic areas for Chagas disease. Am J Trop Med Hyg 2010; 82:580-2. [PMID: 20348502 DOI: 10.4269/ajtmh.2010.09-0397] [Citation(s) in RCA: 24] [Impact Index Per Article: 1.6] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/07/2022] Open
Abstract
The epidemiology of Chagas disease was studied in five rural communities located in the eastern region of the Panama Province. Serological tests for Trypanosoma cruzi infection revealed a prevalence of 5.88% (12/204). Hemocultures coupled with polymerase chain reaction (PCR) analysis showed a Trypanosoma rangeli infection rate of 5.88% (12/204). An overall trypanosome infection index of 11.76% (24/204) was detected in this population. A total of 121 triatomine specimens were collected in domestic and peridomestic habitats. Rhodnius pallescens was confirmed as the predominant species. Molecular analysis showed that 17.8% (13/73) of the examined insects were positive for T. cruzi, 17.8% (13/73) for T. rangeli, and 35.6% (26/73) presented mixed infections. Among 73 R. pallescens evaluated, 16.4% (12/73) contained opossum blood meals. The epidemiological implications of these findings are discussed.
Collapse
Affiliation(s)
- José E Calzada
- Gorgas Memorial Institute of Health Studies, Panama, Republic of Panama.
| | | | | | | | | | | |
Collapse
|
|
21
|
de Moraes MH, Guarneri AA, Girardi FP, Rodrigues JB, Eger I, Tyler KM, Steindel M, Grisard EC. Different serological cross-reactivity of Trypanosoma rangeli forms in Trypanosoma cruzi-infected patients sera. Parasit Vectors 2008; 1:20. [PMID: 18611261 PMCID: PMC2475519 DOI: 10.1186/1756-3305-1-20] [Citation(s) in RCA: 30] [Impact Index Per Article: 1.8] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/11/2008] [Accepted: 07/08/2008] [Indexed: 11/20/2022] Open
Abstract
UNLABELLED BACKGROUND American Trypanosomiasis or Chagas disease is caused by Trypanosoma cruzi which currently infects approximately 16 million people in the Americas causing high morbidity and mortality. Diagnosis of American trypanosomiasis relies on serology, primarily using indirect immunofluorescence assay (IFA) with T. cruzi epimastigote forms. The closely related but nonpathogenic Trypanosoma rangeli has a sympatric distribution with T. cruzi and is carried by the same vectors. As a result false positives are frequently generated. This confounding factor leads to increased diagnostic test costs and where false positives are not caught, endangers human health due to the toxicity of the drugs used to treat Chagas disease. RESULTS In the present study, serologic cross-reactivity between the two species was compared for the currently used epimastigote form and the more pathologically relevant trypomastigote form, using IFA and immunoblotting (IB) assays. Our results reveal an important decrease in cross reactivity when T. rangeli culture-derived trypomastigotes are used in IFA based diagnosis of Chagas disease. Western blot results using sera from both acute and chronic chagasic patients presenting with cardiac, indeterminate or digestive disease revealed similar, but not identical, antigenic profiles. CONCLUSION This is the first study addressing the serological cross-reactivity between distinct forms and strains of T. rangeli and T. cruzi using sera from distinct phases of the Chagasic infection. Several T. rangeli-specific proteins were detected, which may have potential as diagnostic tools.
Collapse
Affiliation(s)
- Milene H de Moraes
- Departamento de Microbiologia e Parasitologia, Universidade Federal de Santa Catarina, 88040-900, Florianópolis, Santa Catarina, Brazil
| | - Alessandra A Guarneri
- Departamento de Microbiologia e Parasitologia, Universidade Federal de Santa Catarina, 88040-900, Florianópolis, Santa Catarina, Brazil
- Instituto René Rachou, Fiocruz, Belo Horizonte, Minas Gerais, Brazil
| | - Fabiana P Girardi
- Departamento de Microbiologia e Parasitologia, Universidade Federal de Santa Catarina, 88040-900, Florianópolis, Santa Catarina, Brazil
| | - Juliana B Rodrigues
- Departamento de Microbiologia e Parasitologia, Universidade Federal de Santa Catarina, 88040-900, Florianópolis, Santa Catarina, Brazil
| | - Iriane Eger
- Departamento de Microbiologia e Parasitologia, Universidade Federal de Santa Catarina, 88040-900, Florianópolis, Santa Catarina, Brazil
- Universidade do Vale do Itajaí, Itajaí, Santa Catarina, Brazil
| | - Kevin M Tyler
- Biomedical Research Centre, School of Medicine, Health Policy and Practice, University of East Anglia, Norwich, Norfolk, UK
| | - Mário Steindel
- Departamento de Microbiologia e Parasitologia, Universidade Federal de Santa Catarina, 88040-900, Florianópolis, Santa Catarina, Brazil
| | - Edmundo C Grisard
- Departamento de Microbiologia e Parasitologia, Universidade Federal de Santa Catarina, 88040-900, Florianópolis, Santa Catarina, Brazil
- Biomedical Research Centre, School of Medicine, Health Policy and Practice, University of East Anglia, Norwich, Norfolk, UK
| |
Collapse
|
|
22
|
Diez H, Sarmiento L, Caldas ML, Montilla M, Thomas MDC, Lopez MC, Puerta C. Cellular location of KMP-11 protein in Trypanosoma rangeli. Vector Borne Zoonotic Dis 2008; 8:93-6. [PMID: 18171105 DOI: 10.1089/vbz.2006.0650] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/12/2022] Open
Abstract
We describe the localization of the KMP-11 protein in the Trypanosoma rangeli parasite determined by immunoelectron microscopy using a monoclonal antibody generated against the Trypanosoma cruzi KMP-11 protein. The data reported herein show that the T. rangeli KMP-11 protein is mainly accumulated in the parasite cytoplasm, the coat, the flagellum, and the flagellar pocket. The high degree of sequence homology between the KMP-11 proteins from both parasites suggests that the KMP-11 protein from T. rangeli, like that of T. cruzi, could also be associated with the parasite cytoskeleton.
Collapse
Affiliation(s)
- Hugo Diez
- Laboratorio de Parasitología Molecular, Pontificia Universidad Javeriana, Bogotá, Colombia
| | | | | | | | | | | | | |
Collapse
|
|
23
|
Basso B, Moretti E, Fretes R. Vaccination with epimastigotes of different strains of Trypanosoma rangeli protects mice against Trypanosoma cruzi infection. Mem Inst Oswaldo Cruz 2008; 103:370-4. [DOI: 10.1590/s0074-02762008000400010] [Citation(s) in RCA: 21] [Impact Index Per Article: 1.2] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/04/2008] [Accepted: 06/12/2008] [Indexed: 11/22/2022] Open
|
|
24
|
Cardillo F, Postol E, Nihei J, Aroeira LS, Nomizo A, Mengel J. B cells modulate T cells so as to favour T helper type 1 and CD8+ T-cell responses in the acute phase of Trypanosoma cruzi infection. Immunology 2007; 122:584-95. [PMID: 17635611 PMCID: PMC2266037 DOI: 10.1111/j.1365-2567.2007.02677.x] [Citation(s) in RCA: 40] [Impact Index Per Article: 2.2] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/11/2022] Open
Abstract
In this study, we have evaluated the production of pro- and anti-inflammatory cytokines and the formation of central and effector memory T cells in mice lacking mature B cells (mu MT KO). The results show that Trypanosoma cruzi infection in C57Bl/6m mu MT KO mice is intensified in relation to control mice and this exacerbation is related to low levels of inflammatory cytokines produced during the acute infection and the lower numbers of central and effector memory CD4(+) and CD8(+) T cells generated during the acute phase of the infection. In addition, a marked reduction in the CD8(+) T-cell subpopulation was observed in mu MT KO infected mice. In agreement to this, the degree of tissue parasitism was increased in mu MT mice and the tissue inflammatory response was much less intense in the acute phase of the infection, consistent with a deficit in the generation of effector T cells. Flow cytometry analysis of the skeletal muscle inflammatory infiltrate showed a predominance of CD8(+) CD45Rb low in B-cell-sufficient C57Bl/6 mice, whereas the preponderant cell type in mu MT KO skeletal muscle inflammatory infiltrate was CD4(+) T cells. In addition, CD8(+) T cells found in skeletal muscle from mu MT KO infected mice were less activated than in control B-cell sufficient infected mice. These results suggest that B cells may participate in the generation of effector/memory T cells. In addition and more importantly, B cells were crucial in the maintenance of central and effector memory CD8(+) T cell, as well as the determination of the T cell cytokine functional pattern, and they may therefore account for critical aspects of the resistance to intracellular pathogens, such as T. cruzi.
Collapse
Affiliation(s)
- Fabiola Cardillo
- Cellular Immunology, Autoimmunity and Experimental Chagas Disease Laboratory, Oswaldo Cruz Foundation, Gonçalo Moniz Research CenterSalvador, Bahia, Brazil
| | - Edilberto Postol
- Immunology Laboratory, Heart Institute (INCOR), University of São PauloSão Paulo, SP, Brazil
| | - Jorge Nihei
- Cellular Immunology, Autoimmunity and Experimental Chagas Disease Laboratory, Oswaldo Cruz Foundation, Gonçalo Moniz Research CenterSalvador, Bahia, Brazil
| | | | - Auro Nomizo
- Department of Clinical Analysis, Toxicology and Bromatology, Faculty of Pharmaceutical Sciences of Ribeirão Preto, University of São PauloBrazil
| | - José Mengel
- Cellular Immunology, Autoimmunity and Experimental Chagas Disease Laboratory, Oswaldo Cruz Foundation, Gonçalo Moniz Research CenterSalvador, Bahia, Brazil
| |
Collapse
|
|
25
|
Basso B, Castro I, Introini V, Gil P, Truyens C, Moretti E. Vaccination with Trypanosoma rangeli reduces the infectiousness of dogs experimentally infected with Trypanosoma cruzi. Vaccine 2007; 25:3855-8. [PMID: 17349724 PMCID: PMC7127752 DOI: 10.1016/j.vaccine.2007.01.114] [Citation(s) in RCA: 32] [Impact Index Per Article: 1.8] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/24/2006] [Revised: 12/27/2006] [Accepted: 01/29/2007] [Indexed: 11/18/2022]
Abstract
The goal of this work was to test the efficacy of the vaccination with Trypanosoma rangeli in dogs. Mongrel dogs received three subcutaneous injections of fixed T. rangeli epimastigotes at 6-week intervals. Such immunisation induced antibodies against Trypanosoma cruzi. While both control and immunised dogs developed detectable parasitemia, this was lower and shorter in vaccinated animals. Interestingly, feeding of Triatoma infestans nymphs on vaccinated and chronically infected dogs led to a sharp reduction in the rate of bug infection. These results suggest that it might be possible to reduce the vectorial parasitemia through vaccination of dogs. As dogs are known to play a major role in the domestic cycle of T. cruzi, this might represent a strategy to reduce parasite transmission to humans.
Collapse
Affiliation(s)
- Beatriz Basso
- Facultad de Ciencias Médicas, Universidad Nacional de Córdoba & Servicio Nacional de Chagas, Córdoba, Argentina.
| | | | | | | | | | | |
Collapse
|
|
26
|
Cuervo C, López MC, Puerta C. The Trypanosoma rangeli histone H2A gene sequence serves as a differential marker for KP1 strains. INFECTION GENETICS AND EVOLUTION 2006; 6:401-9. [PMID: 16504597 DOI: 10.1016/j.meegid.2006.01.005] [Citation(s) in RCA: 12] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Received: 06/29/2005] [Revised: 01/16/2006] [Accepted: 01/19/2006] [Indexed: 11/29/2022]
Abstract
Trypanosoma rangeli has recently been divided in two primary lineages denoted as KP1(+) and KP1(-) strains because of epidemiological and evolutionary interest in the molecular differentiation of these two groups. We report the molecular characterization of the genes encoding histone H2A protein from a T. rangeli KP1(+) strain (H14), its comparison to T. rangeli KP1(-) strain (C23) histone H2A coding genes [Puerta, C., Cuervo, P., Thomas, M.C., López, M.C., 2000. Molecular characterization of the histone H2A gene from the parasite Trypanosoma rangeli. Parasitol. Res. 86, 916-922], and its application in a low-stringency single specific primer polymerase chain reaction (LSSP-PCR) assay to differentiate these parasite groups. The results show that the locus encoding the H2A protein in the H14 strain is formed by at least 11 gene units measuring 799 nucleotides in length, organized in tandem, and located in two chromosomes of approximately 1.9 and 1.1Mb in size. Remarkably, in KP1(-) strains these genes are on pairs of chromosomes of about 1.7 and 1.9Mb. In addition, there is a hybridization signal in the compression region above 2.1Mb in all T. rangeli strains. Therefore, the chromosomal location of these genes is a useful marker to distinguish between KP1(+) and KP1(-) T. rangeli strains. The alignment of the H2A nucleotide sequences from H14 and C23 strains showed an identity of 99.5% between the coding regions and an identity of 95% between the non-coding regions. The deduced amino acid sequences proved to be identical. Based on 5% of the difference between the intergenic regions, we developed a LSSP-PCR assay which can differentiate between KP1(+) and KP1(-) strains.
Collapse
Affiliation(s)
- Claudia Cuervo
- Laboratorio de Parasitología Molecular, Departamento de Microbiología, Facultad Ciencias, Universidad Javeriana, Carrera 7 No. 43-82, Edificio 50, Laboratorio 113, Bogotá, Colombia
| | | | | |
Collapse
|