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Reliable and Sensitive Nested PCR for the Detection of Chlamydia in Sputum. Microorganisms 2021; 9:microorganisms9050935. [PMID: 33925646 PMCID: PMC8145989 DOI: 10.3390/microorganisms9050935] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/14/2021] [Revised: 04/25/2021] [Accepted: 04/25/2021] [Indexed: 11/16/2022] Open
Abstract
Chlamydia are Gram-negative, intracellular pathogens colonizing epithelial mucosa. They cause primarily atypical pneumonia and have recently been associated with chronic diseases. Diagnostics relies almost exclusively on serological methods; PCR tests are used rarely because in patients with positive ELISA, it is nearly impossible to identify chlamydial DNA. This paradox is associated with DNA degradation in sputum samples, low abundance, and low sensitivity of PCR systems. In a newly designed and validated “nested” PCR (NPCR) assay, it was possible to amplify DNA of Chlamydia known to infect humans in 31% samples. The reliability of the assay was confirmed by DNA sequencing, and all PCR products belonged exclusively to the Chlamydiales, mainly recognized as Chlamydia pneumoniae. Three samples were related to Ca. Rhabdochlamydia porcellionis and Ca. Renichlamydia lutjani, which infect arthropods. In one case, samples were taken from sick individual, indicating the potential as a human pathogen.
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2
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El Yazouli L, Criscuolo A, Hejaji H, Bouazza M, Elmdaghri N, Aroussi Alami A, Amraoui A, Dakka N, Radouani F. Molecular characterisation of Chlamydia pneumoniae associated to atherosclerosis. Pathog Dis 2018; 75:3106323. [PMID: 28387800 DOI: 10.1093/femspd/ftx039] [Citation(s) in RCA: 8] [Impact Index Per Article: 1.1] [Reference Citation Analysis] [Abstract] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/30/2016] [Accepted: 04/05/2017] [Indexed: 11/12/2022] Open
Abstract
Chlamydia pneumoniae is a respiratory pathogen associated with chronic inflammatory diseases such as asthma and atherosclerosis, and its detection in human carotid and coronary atheroma suggests some support for its involvement in atherogenesis. The main objective of our study was to evaluate the association between Chlamydia pneumoniae and atherosclerosis in Moroccan patients through a case-control approach and detected strain genotyping. A total of 137 cases and 124 controls were enrolled, nested PCR was performed for Chlamydia pneumoniae screening of the peripheral blood mononuclear cells (PBMCs) of both cases and controls as well as atheroma plaques from 37 cases, and positive samples were subjected to sequencing for genotyping and phylogenetic analysis. The results showed 54% and 18%, respectively, for positivity in cases and control PBMCs and 86.5% in atheroma plaques, the difference being significant between the two groups (P < 0.001, ORa = 8.580, CI, 95% [3.273-22.491]). Strain sequence analyses showed more than 98% similarity with human reference strains, and revealed various genotypes. This study supports the involvement of Chlamydia pneumoniae in atherosclerosis in the studied population and genotyping revealed that detected strains were identical to human strains circulating worldwide.
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Affiliation(s)
- Loubna El Yazouli
- Chlamydiae and Mycoplasma Laboratory, Institut Pasteur du Maroc, 20360 Casablanca, Morocco.,Biochemistry and Immunology Laboratory, Faculty of Sciences, University Mohamed V Rabat, 10000 Rabat, Morocco
| | - Alexis Criscuolo
- Institut Pasteur - Bioinformatics and Biostatistics Hub - C3BI, USR 3756 IP CNRS, 75724 Paris, France
| | - Hicham Hejaji
- Cardiovascular Surgery Department, CHU Ibn Rochd, 20360 Casablanca, Morocco
| | - Mohamed Bouazza
- Ophthalmology Department, CHU Ibn Rochd, 20360 Casablanca, Morocco
| | - Naima Elmdaghri
- Chlamydiae and Mycoplasma Laboratory, Institut Pasteur du Maroc, 20360 Casablanca, Morocco
| | - Aziz Aroussi Alami
- Cardiovascular Surgery Department, CHU Ibn Rochd, 20360 Casablanca, Morocco
| | | | - Nadia Dakka
- Biochemistry and Immunology Laboratory, Faculty of Sciences, University Mohamed V Rabat, 10000 Rabat, Morocco
| | - Fouzia Radouani
- Chlamydiae and Mycoplasma Laboratory, Institut Pasteur du Maroc, 20360 Casablanca, Morocco
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3
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Sessa R, Pietro MDI, Schiavoni G, Galdiero M, Cipriani P, Romano S, Zagaglia C, Santino I, Faccilongo S, Piano MD. Chlamydia Pneumoniae in Asymptomatic Carotid Atherosclerosis. Int J Immunopathol Pharmacol 2018. [DOI: 10.1177/205873920601900111] [Citation(s) in RCA: 14] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/16/2022] Open
Abstract
We evaluated, in 415 patients with asymptomatic carotid atherosclerosis: (i) the prevalence of C. pneumoniae DNA in atherosclerotic carotid plaques and peripheral blood mononuclear cells (PBMC); (ii) the distribution of C. pneumoniae in atherosclerotic carotid plaques and PBMC from the same patients; (iii) the correlation between circulating anti-chlamydial antibodies and the presence of C. pneumoniae DNA. Overall, 160 atherosclerotic carotid plaques and 174 PBMC specimens from patients with asymptomatic carotid atherosclerosis were examined by ompA nested touchdown PCR for presence of C. pneumoniae. In addition, C. pneumoniae DNA was detected in 81 specimens of atherosclerotic carotid plaque and PBMC obtained from the same patients. C. pneumoniae DNA was found in 36.9% of atherosclerotic carotid plaques and in 40.2% of PBMC specimens examined (P=NS). With regard to 81 patients, C. pneumoniae DNA was detected in 27.2% of atherosclerotic carotid plaques and in 44.4% of PBMC specimens (P=0.05). In 18 patients, the presence of C. pneumoniae DNA in PBMC specimens and atherosclerotic carotid plaques coincided (P=0.005). No statistically significant association was found between anti-C pneumoniae antibodies (IgG and IgA) and positive PCR results. In conclusion, our results suggest that the detection of C. pneumoniae DNA in PBMC specimens seems to be a first-choice method to identify the patients at risk for endovascular chlamydial infection.
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Affiliation(s)
- R. Sessa
- Department of Public Health Sciences, “La Sapienza” University Rome, Italy
| | - M. DI Pietro
- Department of Public Health Sciences, “La Sapienza” University Rome, Italy
| | - G. Schiavoni
- Department of Public Health Sciences, “La Sapienza” University Rome, Italy
| | - M. Galdiero
- Department of Experimental Medicine, Second University of Naples, Naples, Italy
| | - P. Cipriani
- Department of Public Health Sciences, “La Sapienza” University Rome, Italy
| | - S. Romano
- Department of Internal Medicine, Cardiology, University of L'Aquila, Italy
| | - C. Zagaglia
- Department of Public Health Sciences, “La Sapienza” University Rome, Italy
| | - I. Santino
- Department of Public Health Sciences, “La Sapienza” University Rome, Italy
| | - S. Faccilongo
- Department of Public Health Sciences, “La Sapienza” University Rome, Italy
| | - M. Del Piano
- Department of Public Health Sciences, “La Sapienza” University Rome, Italy
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Romano S, Fratini S, Di Pietro M, Schiavoni G, Nicoletti M, Chiarotti F, Del Piano M, Penco M, Sessa R. Chlamydia Pneumoniae Infection in Patients with Acute Coronary Syndrome: A Clinical and Serological 1-Year Follow-Up. Int J Immunopathol Pharmacol 2017; 17:209-18. [PMID: 15171822 DOI: 10.1177/039463200401700213] [Citation(s) in RCA: 8] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/17/2022] Open
Abstract
The role of Chlamydia pneumoniae infection in pathogenesis and prognostic stratification of patients with acute coronary syndromes is still unclear. However, a limitation of many studies is the evaluation of the long-term prognostic role of a sample obtained during the acute phase, whereas the assessment of the temporal trend of antibody titers could be more useful. One-hundred and fourteen consecutive patients with acute coronary syndromes (71 with acute myocardial infarction and 43 with unstable angina) were studied. Blood samples were obtained immediately after hospital admission and 1, 3, 6 and 12 months after the acute event. The microimmunofluorescence test was used to detect C. pneumoniae specific antibodies. The incidence of new coronary events (death, myocardial infarction, recurrent angina) was recorded during the 1-year follow-up period. No significant difference was found between patients with (n = 35) or without (n = 79) new coronary events (N.C.E.) regarding baseline and serial values of C. pneumoniae antibodies. The rate of high titers at any time of follow-up was also similar in the two groups: IgG ≥1:512 were present in 52%, 64%, 55% and 32% of N.C.E.+ patients, and in 48%, 54%, 52% and 36% of N.C.E.- patients at 1, 3, 6 and 12 months respectively; IgA ≥ 1:256 were present in 26%, 23%, 30% and 23% of N.C.E.+ patients and in 20%, 30%, 25% and 19% of N.C.E.- patients at 1, 3, 6 and 12 months respectively. Our data indicate that elevated titers of C. pneumoniae antibodies, even with a serial 1-year evaluation, are not a predictor of future coronary events in patients with acute myocardial infarction or unstable angina.
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Affiliation(s)
- S Romano
- Dept Internal Medicine, Cardiology, University of L'Aquila, L'Aquila, Italy
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5
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Sessa R, Schiavoni G, Di Pietro M, Petrucca A, Cipriani P, Puopolo M, Zagaglia C, Fallucca S, Del Piano M. Chlamydia Pneumoniae in PBMC: Reproducibility of the OMPA Nested Touchdown PCR. Int J Immunopathol Pharmacol 2016; 18:113-20. [PMID: 15698516 DOI: 10.1177/039463200501800112] [Citation(s) in RCA: 9] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/17/2022] Open
Abstract
The aim of our study was to evaluate whether the replicate PCR testing may provide more accurate estimates of C. pneumoniae DNA prevalence in PBMC of patients undergoing carotid endarterectomy. Clinical sensitivity and reproducibility of ompA nested touchdown PCR was also performed. Clinical sensitivity and reproducibility was examined by testing C. pneumoniae-negative PBMC spiked with serial dilutions of semipurified C. pneumoniae elementary bodies (from 8 to 0.002 IFU/ml). Detection of C. pneumoniae DNA was performed by ompA nested touchdown PCR. Each clinical and spiked PBMC DNA specimen was analyzed in replicates of 1,3,5 and 10. PCR results of serial dilutions of C. pneumoniae DNA performed in replicates of 10 were analysed by probit analysis. C. pneumoniae DNA was detected in 14 of the 30 (46.7%) PBMC clinical specimens examined when 10 replicates were tested. When we analyzed 1, 3 and 5 replicates, 4 (13.3%), 7(23.3%), 12(40%) of the 30 specimens were positive, respectively. The limit of detection of ompA nested PCR touchdown was 0.008 IFU/ml when 10 replicates were tested. The ompA nested PCR had reproducibility scores of 10 for 10 from 8 to 4 IFU/ml concentration, but scores decreased for smaller numbers of IFU/ml. Our results showed that repeat testing of the same specimen increased clinical sensitivity as well as reproducibility of the ompA nested touchdown PCR. In conclusion the replicate PCR testing improves the performance of ompA nested touchdown PCR and provides a more accurate estimates of the prevalence of C. pneumoniae in PBMC of patients with atherosclerotic cardiovascular disease.
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Affiliation(s)
- R Sessa
- Department of Public Health Sciences, "La Sapienza" University, Rome, Italy.
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Sessa R, Pietro MD, Filardo S, Turriziani O. Infectious burden and atherosclerosis: A clinical issue. World J Clin Cases 2014; 2:240-249. [PMID: 25032197 PMCID: PMC4097149 DOI: 10.12998/wjcc.v2.i7.240] [Citation(s) in RCA: 64] [Impact Index Per Article: 5.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/27/2013] [Revised: 05/16/2014] [Accepted: 06/11/2014] [Indexed: 02/05/2023] Open
Abstract
Atherosclerotic cardiovascular diseases, chronic inflammatory diseases of multifactorial etiology, are the leading cause of death worldwide. In the last decade, more infectious agents, labeled as “infectious burden”, rather than any single pathogen, have been showed to contribute to the development of atherosclerosis through different mechanisms. Some microorganisms, such as Chlamydia pneumoniae (C. pneumoniae), human cytomegalovirus, etc. may act directly on the arterial wall contributing to endothelial dysfunction, foam cell formation, smooth muscle cell proliferation, platelet aggregation as well as cytokine, reactive oxygen specie, growth factor, and cellular adhesion molecule production. Others, such as Helicobacter pylori (H. pylori), influenza virus, etc. may induce a systemic inflammation which in turn may damage the vascular wall (e.g., by cytokines and proteases). Moreover, another indirect mechanism by which some infectious agents (such as H. pylori, C. pneumoniae, periodontal pathogens, etc.) may play a role in the pathogenesis of atherosclerosis is molecular mimicry. Given the complexity of the mechanisms by which each microorganism may contribute to atherosclerosis, defining the interplay of more infectious agents is far more difficult because the pro-atherogenic effect of each pathogen might be amplified. Clearly, continued research and a greater awareness will be helpful to improve our knowledge on the complex interaction between the infectious burden and atherosclerosis.
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7
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Abstract
We compared five different polymerase chain reaction (PCR) assays for the detection of Chlamydophila pneumoniae DNA using highly purified elementary bodies (EBs) and peripheral blood mononuclear cells (PBMCs) from healthy blood donors. The primers were as follows; two targeting the 16S rRNA gene, one targeting the ompA gene, one targeting the Pst-I gene, and one targeting the 53 kDa outer membrane protein gene. The 16S rRNA touchdown enzyme time release (TETR) PCR, the ompA nested PCR and the 53 kDa nested PCR were the most sensitive assays and could detect one or more EB per assay. These three PCRs also had the same reproducibility, but the minimal amount of C. pneumoniae that could be reproducibly detected (10 of 10 testing positive) was 20 EBs. In a sample of specimens from healthy blood donors, we found 5 of 77 (6.5%) PBMCs specimens to have C. pneumoniae DNA according to the nested ompA PCR. Specimens with the 16S rRNA TETR and 53 kDa nested assays were found to have C. pneumoniae DNA 7 of 77 (9.1%) and 18 of 77 (23.4%) specimens, respectively. The other two assays failed to detect even a single positive. However, the detection rate decreased with repeated testing of the same samples. Our newly designed 53 kDa nested PCR may be as useful as the other four recommended PCR assays and may be a more useful assay for the detection of C. pneumoniae DNA from PBMCs.
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Affiliation(s)
- Hiroshi Fukano
- Division of Respiratory Diseases, Department of Medicine, Kawasaki Medical School, Kurashiki, Okayama, Japan.
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8
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Di Pietro M, Filardo S, De Santis F, Sessa R. Chlamydia pneumoniae infection in atherosclerotic lesion development through oxidative stress: a brief overview. Int J Mol Sci 2013; 14:15105-20. [PMID: 23877837 PMCID: PMC3742290 DOI: 10.3390/ijms140715105] [Citation(s) in RCA: 30] [Impact Index Per Article: 2.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/31/2013] [Revised: 07/04/2013] [Accepted: 07/10/2013] [Indexed: 12/11/2022] Open
Abstract
Chlamydia pneumoniae, an obligate intracellular pathogen, is known as a leading cause of respiratory tract infections and, in the last two decades, has been widely associated with atherosclerosis by seroepidemiological studies, and direct detection of the microorganism within atheroma. C. pneumoniae is presumed to play a role in atherosclerosis for its ability to disseminate via peripheral blood mononuclear cells, to replicate and persist within vascular cells, and for its pro-inflammatory and angiogenic effects. Once inside the vascular tissue, C. pneumoniae infection has been shown to induce the production of reactive oxygen species in all the cells involved in atherosclerotic process such as macrophages, platelets, endothelial cells, and vascular smooth muscle cells, leading to oxidative stress. The aim of this review is to summarize the data linking C. pneumoniae-induced oxidative stress to atherosclerotic lesion development.
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Affiliation(s)
- Marisa Di Pietro
- Department of Public Health and Infectious Diseases, “Sapienza” University, Rome 00185, Italy; E-Mails: (M.D.P.); (S.F.); (F.D.S.)
| | - Simone Filardo
- Department of Public Health and Infectious Diseases, “Sapienza” University, Rome 00185, Italy; E-Mails: (M.D.P.); (S.F.); (F.D.S.)
| | - Fiorenzo De Santis
- Department of Public Health and Infectious Diseases, “Sapienza” University, Rome 00185, Italy; E-Mails: (M.D.P.); (S.F.); (F.D.S.)
| | - Rosa Sessa
- Department of Public Health and Infectious Diseases, “Sapienza” University, Rome 00185, Italy; E-Mails: (M.D.P.); (S.F.); (F.D.S.)
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9
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Lan MY, Chang YY, Chen WH, Tseng YL, Lin HS, Lai SL, Liu JS. Association between MIF gene polymorphisms and carotid artery atherosclerosis. Biochem Biophys Res Commun 2013; 435:319-22. [PMID: 23537651 DOI: 10.1016/j.bbrc.2013.02.129] [Citation(s) in RCA: 17] [Impact Index Per Article: 1.4] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/17/2013] [Accepted: 02/23/2013] [Indexed: 01/08/2023]
Abstract
Atherosclerosis is a chronic inflammatory disorder. Macrophage migration inhibitory factor (MIF) is a potent cytokine that plays an important role in the regulation of immune responses. Polymorphisms including five- to eight-repeat CATT variants ((CATT)(5-8)) and G-173C in the promoter region of the MIF gene are associated with altered levels of MIF gene transcription. The purpose of the study is to investigate the relationship between promoter polymorphisms of the MIF gene and the severity of carotid artery atherosclerosis (CAA). The severity of CAA was assessed in 593 individuals with a history of ischemic stroke by using sonographic examination, and the MIF promoter polymorphisms of these individuals were genotyped. The carriage of (CATT)7 (compared to genotypes composed of (CATT)5, (CATT)6, or both), carriage of C allele (compared to GG), and carriage of the haplotype (CATT)7-C (compared to genotypes composed of (CATT)5-G, (CATT)6-G, or both) were significantly associated with an increase in the severity of CAA. We conclude that polymorphisms in the MIF gene promoter are associated with CAA severity in ischemic stroke patients. These genetic variants may serve as markers for individual susceptibility to CAA.
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Affiliation(s)
- Min-Yu Lan
- Department of Neurology, Kaohsiung Chang Gung Memorial Hospital, Chang Gung University College of Medicine, Niaosong, Kaohsiung 833, Taiwan
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10
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Di Pietro M, De Santis F, De Biase D, Sessa R. The Elusive but Pathogenic Peptidoglycan of Chlamydiae. EUR J INFLAMM 2013. [DOI: 10.1177/1721727x1301100126] [Citation(s) in RCA: 5] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/15/2022] Open
Abstract
Chlamydia species cause a broad spectrum of diseases in humans including severe chronic sequelae related to persistent forms. Despite the lack of detectable amounts of peptidoglycan, several studies suggest the presence of small quantities of peptidoglycan or its derivative at least in some stages of the growth cycle. Based on recent discovery in Chlamydiae of the aminotransferase pathway for biosynthesis of meso-diaminopimelic acid, we demonstrated the up-regulation of the gene (cp0259) encoding L,L-diaminopimelate aminotransferase in chlamydial persistent forms. This finding may be important in the search for target molecules to diagnose and treat Chlamydia-associated chronic diseases.
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Affiliation(s)
- M. Di Pietro
- Department of Public Health and Infectious Diseases, “Sapienza” University, Rome, Italy
| | - F. De Santis
- Department of Public Health and Infectious Diseases, “Sapienza” University, Rome, Italy
| | - D. De Biase
- Department of Medico-Surgical Sciences and Biotechnologies, “Sapienza” University, Latina, Italy
| | - R. Sessa
- Department of Public Health and Infectious Diseases, “Sapienza” University, Rome, Italy
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11
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Fellerhoff B, Wank R. Increased prevalence of Chlamydophila DNA in post-mortem brain frontal cortex from patients with schizophrenia. Schizophr Res 2011; 129:191-5. [PMID: 21546214 DOI: 10.1016/j.schres.2011.04.015] [Citation(s) in RCA: 18] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/21/2010] [Revised: 04/05/2011] [Accepted: 04/14/2011] [Indexed: 01/25/2023]
Abstract
Infection can initiate symptoms of mental illness. It has been shown previously that Chlamydophila DNA is present six times more often in the blood of patients with schizophrenia than in the blood of control individuals. Monocytes, the main targets of Chlamydiaceae infection, are microglia precursors. We identified Chlamydiaceae infection using blinded brain DNA samples derived from the frontal cortex. Using PCR and sequence analysis, we found Chlamydophila DNA to be four times greater in patients with schizophrenia than in controls (schizophrenia: N=34, microbial DNA frequency 23.5%; controls: N=35, microbial DNA frequency 5.7%; P=0.045, OR=5.08). Persistent Chlamydophila-infected microglia or neuronal cells may impair neuronal circuits and thus be a mechanism for causing psychiatric illness in these patients.
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Affiliation(s)
- Barbara Fellerhoff
- Institute of Immunology, University of Munich, Goethestrasse 31, D-80336 Munich, Germany.
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Sessa R, Di Pietro M, Schiavoni G, Macone A, Maras B, Fontana M, Zagaglia C, Nicoletti M, Del Piano M, Morrone S. Chlamydia pneumoniae induces T cell apoptosis through glutathione redox imbalance and secretion of TNF-alpha. Int J Immunopathol Pharmacol 2009; 22:659-68. [PMID: 19822082 DOI: 10.1177/039463200902200311] [Citation(s) in RCA: 18] [Impact Index Per Article: 1.1] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/16/2022] Open
Abstract
Chlamydia pneumoniae persistent infection has been implicated in the pathogenesis of several chronic inflammatory diseases including atherosclerosis, and we hypothesized that modulation of the apoptosis of macrophages and/or T cells by C. pneumoniae infection may contribute to the development of such diseases. We therefore evaluated apoptosis, cytokine response, and redox status in human primary T cells and macrophages infected with C. pneumoniae. In addition, co-cultures of T cells and macrophages infected with C. pneumoniae were also carried out. Apoptosis, and levels of glutathione (GSH), glutathione disulfide (GSSG), and tumour necrosis factor (TNF)-alpha were measured by flow cytometry, high performance liquid chromatography and enzyme-linked immunosorbent assay. C. pneumoniae induced apoptosis in T cells as well as in co-cultures of T cells and infected macrophages by marked decrease in GSH/GSSG ratio and increased production of TNF-alpha, respectively. The results demonstrate that interaction of C. pneumoniae with T cells and/or macrophages characterized by interference with redox status, and secretion of tumour necrosis factor-alpha culminates in the induction of T cell apoptosis and survival of infected macrophages. In conclusion, the inappropriate T cell response against C. pneumoniae and survival of infected macrophages could explain the persistence of this intracellular obligate pathogen in the host-organism; it may contribute to the development of chronic inflammatory diseases, although further studies are needed to clarify such a complex mechanism.
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Affiliation(s)
- R Sessa
- Department of Public Health Sciences, Sapienza University, Rome, Italy
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13
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Nyström-Rosander C, Frisk P, Edvinsson M, Hjelm E, Thelin S, Friman G, Ilbäck NG. Thoracic aortic aneurysm patients with Chlamydophila pneumoniae infection showed a shift in trace element levels in serum and diseased aortic tissue. J Trace Elem Med Biol 2009; 23:100-6. [PMID: 19398057 DOI: 10.1016/j.jtemb.2009.01.002] [Citation(s) in RCA: 7] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/05/2008] [Revised: 11/18/2008] [Accepted: 01/15/2009] [Indexed: 12/19/2022]
Abstract
Few studies have been performed on trace elements in tissues and serum in cardiovascular disease and none in aortic aneurysm. In this study the concentrations of 10 trace elements were determined in serum and aneurysmatic aortic tissue from 23 patients undergoing thoracic surgery. Macroscopically, normal thoracic aortic tissue specimens from 10 forensic autopsies and serum from 23 healthy blood donors served as controls. DNA from the intracellular respiratory pathogen Chlamydophila pneumoniae (C. pneumoniae), which may be involved in the pathogenesis of atherosclerosis, was found in 26% (6/23) of the patients but in none of the controls. The serum copper/zinc ratio, a well-known marker of ongoing infection and/or inflammation, was higher (26%, p<0.001) in aneurysm patients. C. pneumoniae requires iron for its growth. In our aneurysm patients iron was higher in serum (by 54%, p<0.001) and aneurysmal tissue (by 60%, p<0.001). Although calcium was lower in patient sera (by 8%, p<0.001), it tended to be higher (by 20%, ns) in aneurysmatic tissue. In addition, mercury concentrations in serum and aneurysmatic tissue were positively correlated (r=0.51, p<0.05). Moreover, C. pneumoniae-positive aneurysmatic tissues had lower concentrations of manganese (46%, p<0.05) and zinc (26%, ns) but a higher concentration of mercury (50%, p<0.05) than C. pneumoniae-negative aneurysmatic tissues. In conclusion, aneurysm patients showed a shift in trace element levels in serum and in the diseased part of the aorta, the pattern being partly different in C. pneumoniae-positive compared with C. pneumoniae-negative patients. The results are compatible with active infection and/or inflammation, possibly initiated by C. pneumoniae.
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14
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Sessa R, Cipriani P, Di Pietro M, Schiavoni G, Santino I, Del Piano M. Chlamydia Pneumoniae and Chronic Diseases with a Great Impact on Public Health. Int J Immunopathol Pharmacol 2008; 21:1041-3. [DOI: 10.1177/039463200802100431] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/16/2022] Open
Abstract
Chlamydia pneumoniae is recognised as a common cause of respiratory tract infections and has recently been implicated in several extrapulmonary chronic diseases, with great impact on public health, such as atherosclerosis, multiple sclerosis and Alzheimer's disease. The involvement of C. pneumoniae in such diseases may be correlated to characteristic features of this pathogen, including intracellular growth and ability to induce persistent forms. C. pneumoniae persistent forms are inherently more suited to evade the host immune response and are more difficult to eradicate by antibiotics. Our preliminary experimental findings show that interaction of C. pneumoniae with macrophages and/or T cells characterized by interference with TNF-α production, and redox state, culminates in the induction of T cell apoptosis and survival of infected macrophages. Based on our evidence, the poor cooperation between T cells and macrophages could lead to an inappropriate immune response against C. pneumoniae that may therefore promote the development of extrapulmonary chronic diseases.
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Affiliation(s)
- R. Sessa
- Department of Public Health Sciences, Sapienza University, Rome, Italy
| | - P. Cipriani
- Department of Public Health Sciences, Sapienza University, Rome, Italy
| | - M. Di Pietro
- Department of Public Health Sciences, Sapienza University, Rome, Italy
| | - G. Schiavoni
- Department of Public Health Sciences, Sapienza University, Rome, Italy
| | - I. Santino
- Department of Public Health Sciences, Sapienza University, Rome, Italy
| | - M. Del Piano
- Department of Public Health Sciences, Sapienza University, Rome, Italy
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15
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Sessa R, Santino I, Di Pietro M, Schiavoni G, Ripa C, Galdiero M, Iannone M, Izzo L, Mingazzini PI, Bolognese A, Del Piano M. No evidence of involvement of Chlamydia pneumoniae in lung cancer by means of quantitative real-time polymerase chain reaction. Int J Immunopathol Pharmacol 2008; 21:415-20. [PMID: 18547487 DOI: 10.1177/039463200802100221] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Abstract] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/21/2022] Open
Abstract
Chlamydia pneumoniae, an obligate intracellular pathogen, is well-known as etiological agent of acute respiratory infections; the repeated or prolonged exposure to chlamydial antigens may promote the persistence of C. pneumoniae in the respiratory tract leading to chronic diseases, such as chronic obstructive pulmonary disease and asthma. The predilection of C. pneumoniae to cause respiratory tract infections combined with its persistent nature suggest that it might play a role in lung cancer. The aim of our study is to evaluate the involvement of C. pneumoniae in pathogenesis of lung cancer. We therefore investigated the presence of C. pneumoniae DNA in tumor lung tissues by using real-time PCR assay. Simultaneously, tumor and healthy tissues from the same patient with primary carcinoma lung were analyzed. C. pneumoniae DNA was not detected in a single lung tumor tissue by means of an highly sensitive, and specific real-time PCR assay based on FRET hybridization probes. In conclusion, this study does not support the involvement of C. pneumoniae in the pathogenesis of lung cancer, suggesting that further investigations are needed to clarify other potential causative factors for the development of this malignancy.
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Affiliation(s)
- R Sessa
- Department of Public Health Sciences, Sapienza University Rome, Piazzale Aldo Moro 5, Rome, Italy.
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16
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Abstract
Cardiovascular disease, resulting from atherosclerosis, is a leading cause of global morbidity and mortality. Genetic predisposition and classical environmental risk factors explain much of the attributable risk for cardiovascular events in populations, but other risk factors for the development and progression of atherosclerosis, which can be identified and modified, may be important therapeutic targets. Infectious agents, such as Chlamydia pneumoniae, have been proposed as contributory factors in the pathogenesis of atherosclerosis. In the present review, we consider the experimental evidence that has accumulated over the last 20 years evaluating the role of C. pneumoniae in atherosclerosis and suggest areas for future research in this field.
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Edvinsson M, Frisk P, Molin Y, Hjelm E, Ilbäck NG. Trace element balance is changed in infected organs during acute Chlamydophila pneumoniae infection in mice. Biometals 2007; 21:229-37. [PMID: 17712530 DOI: 10.1007/s10534-007-9114-7] [Citation(s) in RCA: 17] [Impact Index Per Article: 0.9] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/07/2006] [Accepted: 08/08/2007] [Indexed: 11/29/2022]
Abstract
Most infectious diseases are accompanied by changed levels of several trace elements in the blood. However, sequential changes in trace elements in tissues harbouring bacterial infections have not been studied. In the present study the respiratory pathogen Chlamydophila pneumoniae (C. pneumoniae), adapted to C57BL/6J mice, was used to study whether the balance of trace elements is changed in infected organs. Bacteria were quantitatively measured by real-time PCR in the blood, lungs, liver, aorta, and heart on days 2, 5, and 8 of the infection. Concentrations of 13 trace elements were measured in the liver, heart, and serum by inductively coupled plasma mass-spectrometry (ICP-MS). Infected mice developed expected clinical signs of disease and bacteria were found in lungs, liver, and heart on all days. The number of bacteria peaked on day 2 in the heart and on day 5 in the liver. The copper/zinc (Cu/Zn) ratio in serum increased as a response to the infection. Cu increased in the liver but did not change in the heart. Iron (Fe) in serum decreased progressively, whereas in the heart it tended to increase, and in the liver it progressively increased. C. pneumoniae may thus cause a changed trace element balance in target tissues of infection that may be pivotal for bacterial growth.
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Affiliation(s)
- Marie Edvinsson
- Department of Medical Sciences, Infectious Diseases, Uppsala University Hospital, Uppsala, Sweden.
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18
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Sessa R, Di Pietro M, Schiavoni G, Petrucca A, Cipriani P, Zagaglia C, Nicoletti M, Santino I, del Piano M. Measurement of Chlamydia pneumoniae bacterial load in peripheral blood mononuclear cells may be helpful to assess the state of chlamydial infection in patients with carotid atherosclerotic disease. Atherosclerosis 2007; 195:e224-30. [PMID: 17575984 DOI: 10.1016/j.atherosclerosis.2007.04.052] [Citation(s) in RCA: 28] [Impact Index Per Article: 1.6] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/20/2007] [Revised: 04/16/2007] [Accepted: 04/27/2007] [Indexed: 02/04/2023]
Abstract
BACKGROUND Chlamydia pneumoniae has been repeatedly associated with atherosclerotic cardiovascular diseases. We investigated the pattern of distribution of C. pneumoniae among patients with carotid atherosclerotic disease evaluating chlamydial load in carotid plaque, peripheral blood mononuclear cells (PBMC) and lymph node from same patient. METHODS AND RESULTS Thirty carotid plaques, 30 PBMC and 30 lymph nodes were examined by real-time PCR assay. C. pneumoniae DNA was detected, in carotid plaques, PBMC and lymph nodes in 11 patients; in carotid plaques and PBMC in five patients; in PBMC and lymph nodes in four patients; in lymph nodes in two patients; and in PBMC only in one patient. C. pneumoniae DNA in PBMC significantly coincided with the presence of the respective DNA in carotid plaque (p=0.0001) and lymph node (p=0.02). A higher chlamydial load was detected in PBMC than in lymph nodes and carotid plaques. More than 90% of patients with carotid plaques, PBMC and lymph nodes positive to C. pneumoniae were symptomatic, smokers, hypertensives, dyslipidemics and showed carotid plaques with rupture on the surface, hemorrhage and thrombosis. CONCLUSION The measurement of chlamydial load in PBMC may be helpful in the future to assess the state of C. pneumoniae infection and the risk of developing sequelae.
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Affiliation(s)
- Rosa Sessa
- Department of Public Health Sciences, Sapienza University, P. le Aldo Moro, 5-00185 Rome, Italy.
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19
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Sessa R, Schiavoni G, Borriello G, Zagaglia C, Marinelli F, del Piano M, Pozzilli C. Real time PCR for detection of Chlamydophila pneumoniae in peripheral blood mononuclear cells of patients with multiple sclerosis. J Neurol 2007; 254:1293-5. [PMID: 17460814 DOI: 10.1007/s00415-006-0504-5] [Citation(s) in RCA: 6] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/06/2006] [Revised: 11/01/2006] [Accepted: 11/05/2006] [Indexed: 10/23/2022]
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20
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Fellerhoff B, Laumbacher B, Mueller N, Gu S, Wank R. Associations between Chlamydophila infections, schizophrenia and risk of HLA-A10. Mol Psychiatry 2007; 12:264-72. [PMID: 17102800 DOI: 10.1038/sj.mp.4001925] [Citation(s) in RCA: 59] [Impact Index Per Article: 3.3] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 01/27/2023]
Abstract
Several microbes have been suspected as pathogenetic factors in schizophrenia. We have previously observed increased frequencies of chlamydial infections and of human lymphocyte antigen (HLA)-A10 in independent studies of schizophrenia. Our aim here was to analyze frequencies of three types of Chlamydiaceae in schizophrenic patients (n=72), random controls (n=225) and hospital-patient controls (n=36), together with HLA-A genotypes. Patients were diagnosed with schizophrenia according to Diagnostic and Statistical Manual of Mental Disorders-IV. Blood samples were collected at the beginning of hospitalization and analyzed with Chlamydiaceae species-specific polymerase chain reaction (PCR). Control panels consisted of randomly selected volunteers and hospitalized, non-schizophrenic patients. We found chlamydial infection in 40.3% of the schizophrenic patients compared to 6.7% in the controls. The association of schizophrenia with Chlamydiaceae infections was highly significant (P=1.39 x 10(-10), odds ratio (OR)=9.43), especially with Chlamydophila psittaci (P=2.81 x 10(-7), OR=24.39). Schizophrenic carriers of the HLA-A10 genotype were clearly most often infected with Chlamydophila, especially C. psittaci (P=8.03 x 10(-5), OR=50.00). Chlamydophila infections represent the highest risk factor yet found to be associated with schizophrenia. This risk is even further enhanced in carriers of the HLA-A10 genotype.
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Affiliation(s)
- B Fellerhoff
- Institute of Immunology, Ludwig-Maximilans University of Munich, Munich, Germany.
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21
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Miyashita N, Obase Y, Fukuda M, Shouji H, Yoshida K, Ouchi K, Oka M. Evaluation of the diagnostic usefulness of real-time PCR for detection of Chlamydophila pneumoniae in acute respiratory infections. J Infect Chemother 2007; 13:183-7. [PMID: 17593507 DOI: 10.1007/s10156-007-0509-8] [Citation(s) in RCA: 16] [Impact Index Per Article: 0.9] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/07/2006] [Accepted: 02/01/2007] [Indexed: 11/24/2022]
Abstract
We investigated whether a real-time polymerase chain reaction (PCR) test is a useful diagnostic tool for identifying individuals with acute respiratory Chlamydophila pneumoniae infections. Nasopharyngeal swab specimens and peripheral blood mononuclear cells (PBMCs) from 100 patients with acute respiratory tract infections and 140 asymptomatic healthy subjects (controls) were analyzed using real-time PCR, culture, and serology for the detection of C. pneumoniae. Six patients had serological results indicating acute C. pneumoniae infections. C. pneumoniae DNA was detected in respiratory samples from eight patients (three of these cases were serologically confirmed as having C. pneumoniae infections) and four controls. The amount of C. pneumoniae DNA present in the real-time PCR for the samples was calculated, and no significant differences in the amount of DNA between symptomatic and asymptomatic subjects were found. On the other hand, traces of C. pneumoniae DNA were detected in PBMCs from eight patients, but this was confirmed in PBMCs from only seven of these patients. Only one patient had both respiratory and blood samples that were positive. C. pneumoniae DNA was also detected in samples from six controls, but no significant differences in the amount of C. pneumoniae DNA were observed between patients and controls. The present quantitative real-time PCR assay does not seem to be a useful method for differentiating between C. pneumoniae acute infections and persistent ones or nasopharyngeal carriage. In addition, the detection of C. pneumoniae DNA in PBMCs does not seem to be a suitable method for the diagnosis of acute respiratory C. pneumoniae infections.
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Affiliation(s)
- Naoyuki Miyashita
- Division of Respiratory Diseases, Department of Medicine, Kawasaki Medical School, 577 Matsushima, Kurashiki, Okayama 701-0192, Japan.
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22
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Kessler W, Jantos CA, Dreier J, Pavlovic S. Chlamydia pneumoniae is not detectable in subretinal neovascular membranes in the exudative stage of age-related macular degeneration. ACTA ACUST UNITED AC 2006; 84:333-7. [PMID: 16704694 DOI: 10.1111/j.1600-0420.2005.00591.x] [Citation(s) in RCA: 12] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/30/2022]
Abstract
PURPOSE Age-related macular degeneration (AMD) is the most frequent cause of severe visual impairment in western countries, but its aetiology remains unclear. A growing body of evidence suggests that inflammation contributes to the pathogenesis of AMD, similarly to that shown for atherosclerosis. In view of a number of shared risk factors between the two entities and the hypothesized link between Chlamydia pneumoniae infection and atherosclerosis, we investigated whether C. pneumoniae might be involved in exudative AMD. METHODS To examine whether C. pneumoniae contributes to the development of subretinal neovascular (SRNV) membranes in AMD, 13 consecutive SRNV membranes surgically excised from patients with exudative AMD were collected and assayed for the presence of C. pneumoniae or other bacterial pathogens by means of polymerase chain reaction (PCR). RESULTS The age of patients ranged from 68 to 85 years (median 73.5 years). In all 13 SRNV membranes, no DNA of either C. pneumoniae or other pathogens was found by PCR. CONCLUSIONS These findings indicate that C. pneumoniae is not associated with the development of SRNV membranes in exudative AMD.
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Affiliation(s)
- Werner Kessler
- Department of Opthalmology, University of Giessen, Giessen, Germany.
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23
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Ikejima H, Friedman H, Leparc GF, Yamamoto Y. Depletion of resident Chlamydia pneumoniae through leukoreduction by filtration of blood for transfusion. J Clin Microbiol 2005; 43:4580-4. [PMID: 16145110 PMCID: PMC1234142 DOI: 10.1128/jcm.43.9.4580-4584.2005] [Citation(s) in RCA: 6] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/20/2022] Open
Abstract
Current studies indicate that a significant percentage of healthy blood donors carry Chlamydia pneumoniae in their blood. Although the clinical significance of such findings is unknown, eradication of such bacteria from blood components may contribute to transfusion safety. Deletion of C. pneumoniae in Red Blood Cell (RBC) units was accomplished through leukoreduction by filtration. The presence of bacteria in RBC units before and after leukoreduction was assessed by real-time PCR using primers specific for C. pneumoniae 16S rRNA. The eluates of filters used for leukoreduction were also assessed by PCR and immunostaining with fluorescein isothiocyanate-conjugated chlamydial monoclonal antibodies specific for C. pneumoniae determination. Nineteen of 30 RBC units tested showed the presence of C. pneumoniae DNA. Leukofiltration resulted in a marked reduction of leukocytes as well as C. pneumoniae in terms of bacterial number and positive rate for the bacteria. The eluates of filters showed trapped bacteria determined by both PCR and immunostaining assays. Thus, leukoreduction with a filter is an effective method to significantly reduce resident C. pneumoniae levels in RBC components but may not be completely sufficient for total eradication of this pathogen.
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Affiliation(s)
- Hideaki Ikejima
- Department of Medical Microbiology and Immunology, University of South Florida College of Medicine, Tampa, 33612, USA
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24
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Fellerhoff B, Laumbacher B, Wank R. High risk of schizophrenia and other mental disorders associated with chlamydial infections: hypothesis to combine drug treatment and adoptive immunotherapy. Med Hypotheses 2005; 65:243-52. [PMID: 15922095 DOI: 10.1016/j.mehy.2005.03.013] [Citation(s) in RCA: 32] [Impact Index Per Article: 1.6] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/06/2005] [Accepted: 03/02/2005] [Indexed: 12/29/2022]
Abstract
Many microbial factors have been implicated as pathogenic factors in mental disorders. Occurrence of such microbial factors also in the mentally unaffected population raised skepticism against such findings, although each microbial factor may cause mental problems only in some individuals, depending on the individual's immunogenetic disposition. Skepticism against the role of infection in schizophrenia was also fostered by the low impact of antiinfections treatment on the course of disease progression in schizophrenia. We discovered previously that neurotrophins like neurotrophin3 (NT-3) and brain-derived neurotrophic factor (BDNF), involved in processes of neuroplasticity, are also secreted by immune cells, but only by subpopulations of immune cells. Therefore, infection of the immune cell subpopulation, specialized in secreting BDNF, or of another subpopulation, specialized in secreting NT-3, could distort communication of immune cells with the central nervous system (CNS). Chlamydiaceae could cause disbalancement of immune cell sub-populations and, in some individuals with a vulnerable disposition, symptoms of mental illness. Based on previous observations of persisting IgA titers in some patients with mental illness we hypothesize that the intracellular parasites Chlamydiaceae are main pathogenic factors in schizophrenia. We hypothesize furthermore that antiinfectious treatment has to be accompanied by adoptive immunotherapy because antibiotics alone will not restore the balance of immune subpopulations. Our hypothesis is supported by examination of patients with schizophrenia and other mental disorders. Using nested PCR we found a significant prevalence of the intracellular parasites Chlamydophila psittaci, C. pneumoniae and Chlamydia trachomatis (9/18, 50%), as compared to controls (8/115, 6.97%) (chi(2)=25.86, Fisher's exact p two-tailed=5x10(-5)). Treatment with in vitro-activated immune cells together with antibiotic modalities showed sustained mental improvements in patients that did not depend on treatment with antipsychotic drugs. Future controlled studies including sham treatment of patients have to be carried out to prove our hypotheses.
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Affiliation(s)
- Barbara Fellerhoff
- Institute of Immunology, Ludwig Maximilians-Universitaet Muenchen, Goethestrasse 31, D-80336 Muenchen, Germany
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25
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Chatzipanagiotou S, Tsakanikas C, Anagnostouli M, Rentzos M, Ioannidis A, Nicolaou C. Detection of Chlamydia pneumoniae in the cerebrospinal fluid of patients with multiple sclerosis by combination of cell culture and PCR: no evidence for possible association. ACTA ACUST UNITED AC 2005; 7:41-3. [PMID: 14529319 DOI: 10.1007/bf03260019] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.1] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 10/27/2022]
Abstract
BACKGROUND During the course of multiple sclerosis (MS) intrathecal oligoclonal IgGs are present in the cerebrospinal fluid (CSF). The intracellular human pathogen Chlamydia pneumoniae may play a role either as a causative pathogenetic agent in the disease, or C. pneumoniae-infected MS patients could be immunologically less able to clear the agent from the central nervous system (CNS). METHODS CSF samples were studied in 100 individuals -- 70 MS patients and 30 age-matched controls with other neurological diseases. CSF was taken by lumbal puncture; cell cultures were performed by the cell vial technique, followed by a 4-day incubation at 37 degrees C. A nested PCR was performed. RESULTS C. pneumoniae was detectable in the CSF of only 2.9% of the MS patients and none of control patients (with no significant difference between the MS patients and controls). IgG antibodies were positive in only 1.43% of the MS patients and 3.33% of the controls. IgA antibodies were positive in 6.66% of the control patients and none of the patients were positive for IgM antibodies. There was no statistically significant difference between the two groups of patients with respect to the three antibody classes. CONCLUSIONS The results confirm the high leave of controversy surrounding a possible link between C. pneumoniae and MS, and the matter requires further thorough investigation.
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Sessa R, Di Pietro M, Schiavoni G, Santino I, Del Piano M. Could Chlamydia Pneumoniae Be Considered an Infectious Risk Factor for Inflammatory Diseases Such as Atherosclerosis ? EUR J INFLAMM 2005. [DOI: 10.1177/1721727x0500300301] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/17/2022] Open
Abstract
Chlamydia pneumoniae, a Gram-negative intracellular obligate bacteria, is recognised as a common cause of upper respiratory tract infections, and accounts for ∼10% of community-acquired pneumonia. In recent years, chronic and persistent infection with C. pneumoniae has been implicated in the pathogenesis of atherosclerosis. Atherosclerosis is regarded as a chronic inflammatory disease that results from complex interactions between a variety of cell types such as endothelial cells, vascular smooth muscle cells, monocytes/macrophages and inflammatory mediators. Involvement of C. pneumoniae in the pathogenesis of atherosclerosis has been supported by findings from seroepidemiologic studies, direct detection of chlamydial DNA, experimental animal and in vitro studies, and antibiotic intervention trials. The spectrum of cell biological, animal, and human clinical data suggests that C. pneumoniae may be considered an infectious risk factor for atherosclerosis but further studies are needed to clarify the etiopathogenetic role of C. pneumoniae in atherosclerotic vessel walls.
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Affiliation(s)
- R. Sessa
- Department of Public Health Sciences - “La Sapienza” University, Rome
| | - M. Di Pietro
- Department of Public Health Sciences - “La Sapienza” University, Rome
| | - G. Schiavoni
- Department of Public Health Sciences - “La Sapienza” University, Rome
| | - I. Santino
- Department of Public Health Sciences - “La Sapienza” University, Rome
| | - M. Del Piano
- Department of Public Health Sciences - “La Sapienza” University, Rome
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Cochrane M, Walker P, Gibbs H, Timms P. Multiple genotypes of Chlamydia pneumoniae identified in human carotid plaque. Microbiology (Reading) 2005; 151:2285-2290. [PMID: 16000718 DOI: 10.1099/mic.0.27781-0] [Citation(s) in RCA: 23] [Impact Index Per Article: 1.2] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/18/2022] Open
Abstract
Chlamydia pneumoniae is an obligate intracellular respiratory pathogen that causes 10 % of community-acquired pneumonia and has been associated with cardiovascular disease. Both whole-genome sequencing and specific gene typing suggest that there is relatively little genetic variation in human isolates of C. pneumoniae. To date, there has been little genomic analysis of strains from human cardiovascular sites. The genotypes of C. pneumoniae present in human atherosclerotic carotid plaque were analysed and several polymorphisms in the variable domain 4 (VD4) region of the outer-membrane protein-A (ompA) gene and the intergenic region between the ygeD and uridine kinase (ygeD–urk) genes were found. While one genotype was identified that was the same as one reported previously in humans (respiratory and cardiovascular), another genotype was found that was identical to a genotype from non-human sources (frog/koala).
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Affiliation(s)
- Melanie Cochrane
- School of Life Sciences, Queensland University of Technology, GPO Box 2434, Brisbane, Australia
| | - Philip Walker
- University of Queensland, Department of Surgery, Royal Brisbane Hospital, Brisbane, Australia
| | - Harry Gibbs
- Princess Alexandra Hospital, Brisbane, Australia
| | - Peter Timms
- School of Life Sciences, Queensland University of Technology, GPO Box 2434, Brisbane, Australia
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28
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Rupp J, Koch M, van Zandbergen G, vanZandbergen G, Solbach W, Brandt E, Maass M. Transmission of Chlamydia pneumoniae infection from blood monocytes to vascular cells in a novel transendothelial migration model. FEMS Microbiol Lett 2005; 242:203-8. [PMID: 15621438 DOI: 10.1016/j.femsle.2004.11.010] [Citation(s) in RCA: 14] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/07/2004] [Revised: 10/12/2004] [Accepted: 11/02/2004] [Indexed: 11/25/2022] Open
Abstract
Chlamydia pneumoniae uses blood monocytes (PBMC) for systemic dissemination, persists in atherosclerotic lesions, and has been implicated in the pathogenesis of atherosclerosis. During transmigration in a newly developed transendothelial migration model (TEM) C. pneumoniae-infected PBMC spread their infection to endothelial cells. Transmigrated PBMC retained their infectivity and transmitted the pathogen to smooth muscle cells in the lower chamber of the TEM. Detection of chlamydial HSP60 mRNA proved pathogen viability and virulence. We conclude that PBMC can spread chlamydial infection to vascular wall cells and we suggest the TEM as a novel tool to analyze host-pathogen interactions in vascular chlamydial infections.
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Affiliation(s)
- Jan Rupp
- Institute of Medical Microbiology and Hygiene, University of Luebeck, Ratzeburger Allee 160, 23560 Luebeck, Germany
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29
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Sessa R, Di Pietro M, Ratanarat R, Rassu M, Ronco C. Chlamydia pneumoniae as risk factor of cardiovascular disease in dialysis patients. Int J Artif Organs 2005; 28:3-7. [PMID: 15742303 DOI: 10.1177/039139880502800102] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.1] [Reference Citation Analysis] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/15/2022]
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30
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Sessa R, Di Pietro M, Schiavoni G, Nicoletti M, Soda G, Nardoni S, Bosco D, Santino I, Cipriani P, Del Piano M. Detection of Chlamydia pneumoniae in atherosclerotic coronary arteries. Int J Immunopathol Pharmacol 2005; 17:301-6. [PMID: 15461864 DOI: 10.1177/039463200401700310] [Citation(s) in RCA: 23] [Impact Index Per Article: 1.2] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/17/2022] Open
Abstract
Chlamydia pneumoniae has recently been associated with the development of coronary heart diseases by sero-epidemiological studies and by direct detection of the organism in atherosclerotic tissues. The aim of our study was to employ a semi-nested PCR approach to investigate the presence of C. pneumoniae in both normal and atherosclerotic coronary arteries of humans obtained at autopsy. Moreover, we have evaluated the role of infection with C. pneumoniae in relation to the extent of coronary atherosclerosis. One hundred and eighty coronary artery specimens were collected at autopsy from 60 consecutive subjects (three arterial segments from each subject). Atherosclerosis in each arterial segment was graded histologically by the Stary classification. Thirty normal coronary arteries were also taken at autopsy as control. PCR results evidenced the presence of C. pneumoniae DNA in atherosclerotic coronary arteries in 19 (31.7%) of 60 subjects examined, while none of the 30 subjects with non-atherosclerotic tissues was positive (p=0.001). Moreover, of the 180 atherosclerotic specimens examined, C. pneumoniae DNA was detected in 3.4% (2/59) of mild atherosclerotic lesions, and in 14.0% (17/121) of advanced atherosclerotic lesions (p=0.05). Our results demonstrate that the presence of C. pneumoniae DNA may be associated with the severity of coronary atherosclerosis.
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Affiliation(s)
- R Sessa
- Dipartimento di Scienze di Sanità Pubblica, University of Rome, La Sapienza, Rome, Italy.
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31
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Mitusch R, Luedemann J, Wood WG, Berger K, Schminke U, Suter M, Kessler C, John U, Rupp J, Kentsch M, Maass M. Asymptomatic carotid atherosclerosis is associated with circulating chlamydia pneumoniae DNA in younger normotensive subjects in a general population survey. Arterioscler Thromb Vasc Biol 2004; 25:386-91. [PMID: 15550694 DOI: 10.1161/01.atv.0000151284.49967.a7] [Citation(s) in RCA: 10] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/16/2022]
Abstract
OBJECTIVE Chlamydia pneumoniae infection has been associated with atherosclerosis, but serodiagnosis is unreliable in predicting vascular infection. Direct detection of circulating chlamydial DNA in peripheral blood mononuclear cells (PBMCs) was thus evaluated as a marker for cardiovascular risk in a general population survey using the common carotid intima-media thickness (IMT) as surrogate marker of asymptomatic atherosclerosis. METHODS AND RESULTS C pneumoniae DNA in PBMCs was determined by nested polymerase chain reaction and associated with IMT for 1032 healthy participants of a general population survey who were within the highest or lowest IMT distribution quartile. C pneumoniae DNA was more prevalent in those with increased IMT (13.4% versus 10.7%), but this was not significant in univariate and of borderline significance in multivariate analysis. Testing for potential effect modifications by known strong determinants of an increased IMT in group interaction analysis revealed an independent association between C pneumoniae DNA and IMT in normotensive subjects (odds ratio [OR], 2.06; 95% CI, 1.05 to 4.03; P=0.04) and in those <70 years old (OR, 1.84; 95% CI, 1.06 to 3.19; P=0.03). CONCLUSIONS Asymptomatic atherosclerosis is associated with circulating C pneumoniae DNA independently of classical cardiovascular risk factors in normotensive subjects and those <70 years old. C pneumoniae has been implicated in atherogenesis. We determined the association of chlamydial DNA in peripheral blood mononuclear cells with the carotid intima-media thickness from 1032 healthy subjects from a general population survey. A stratified group interaction analysis revealed an independent association in normotensive subjects and those <70 years old.
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Affiliation(s)
- Rolf Mitusch
- Medical Department, Hanse-Hospital Stralsund, Teaching Hospital of the Ernst-Moritz-Arndt-University of Greifswald, Post Box 2341, D-18410 Stralsund, Germany.
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32
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Krausse-Opatz B, Schmidt C, Fendrich U, Bialowons A, Kaever V, Zeidler H, Kuipers J, Köhler L. Production of prostaglandin E2 in monocytes stimulated in vitro by Chlamydia trachomatis, Chlamydophila pneumoniae, and Mycoplasma fermentans. Microb Pathog 2004; 37:155-61. [PMID: 15351039 DOI: 10.1016/j.micpath.2004.06.007] [Citation(s) in RCA: 12] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/22/2004] [Revised: 06/10/2004] [Accepted: 06/29/2004] [Indexed: 10/26/2022]
Abstract
Chlamydia trachomatis (CT) as well as Chlamydophila pneumoniae (CP) cause chronic inflammatory diseases in humans. Persistently infected monocytes are involved in the pathogenesis by inducing mediators of inflammation. An in vitro system of chlamydial persistence in human peripheral blood monocytes (HPBM) was used to investigate prostaglandin E(2) (PGE(2)) production and the expression of the key enzyme for prostaglandin production, cyclooxygenase-2 (COX-2). PGE(2) production was determined by PGE(2)-ELISA of HPBM-culture supernatants. Cox-2 mRNA expression was measured by real-time RT-PCR of total RNA isolated from HPBM. Both, CT and CP, stimulated PGE(2) production of HPBM in vitro. Equivalent numbers of CT per host cell induced a higher PGE(2)-response compared to CP. The amount of synthesized PGE(2) depended on the chlamydial multiplicity of infection (MOI). Even at an MOI of 10 the amount of CT- and CP-induced prostaglandin, respectively, was lower than the amount of prostaglandin induced by E. coli lipopolysaccharide (LPS) at a concentration of 10microg/ml. In contrast to stimulation with LPS, Chlamydia-induced PGE(2) production as well as cox-2 mRNA decreased after day 1 post infection (p.i.). These data indicate that Chlamydia stimulate PGE(2) production in human monocytes. Since Chlamydia are often contaminated by mycoplasma, the influence of mycoplasma on the prostaglandin production was investigated additionally. Mycoplasma fermentans (MF) also stimulated PGE(2) production. The co-infection of mycoplasma and Chlamydia resulted in an additive effect in the production of PGE(2). Thus it is important to use host cells and Chlamydia free of mycoplasma contamination for the analysis of Chlamydia-induced prostaglandin production.
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Affiliation(s)
- Birgit Krausse-Opatz
- Division of Rheumatology, Department of Internal Medicine, Carl-Neuberg-Str. 1, D-30625 Hannover, Germany.
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Gutiérrez J, Linares J, Fernández F, Ros E, Luna JDD, Mendoza J, Soto MJ, López C, Maroto C. [Relationship between the peripheral arterial occlusive disease and the infection by Chlamydophila pneumoniae]. Med Clin (Barc) 2004; 123:561-6. [PMID: 15535936 DOI: 10.1016/s0025-7753(04)74598-4] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/30/2022]
Abstract
BACKGROUND AND OBJECTIVE The relationship between peripheral arterial occlusive disease (PAOD) and Chlamydophila pneumoniae infection was studied by analyzing clinical samples from 95 patients with PAOD (cases) and 100 controls. PATIENTS AND METHOD The following investigations were conducted: IgG and IgA against lipopolysaccharide (LPS) and against purified C. pneumoniae-specific antigens from elementary bodies (EB) with ELISA; anti-EB IgG, with MIF; C. pneumoniae DNA in arterial biopsy and peripheral blood leukocyte cells (PBLCs) with heminested PCR; LPS with ELISA; and bacteria culture in HEp-2 cells from arterial biopsy. RESULTS The percentage of positive results in cases and controls groups for anti-LPS IgG was: 21% and 14%, respectively, with no differences; nor were there any differences with IgA (22 and 21%, respectively). However, differences were seen in the anti-EB IgG between cases (74% and 72%, for ELISA and MIF, respectively) and controls (31% and 34%). There were no differences in anti-EB IgA. Bacterial DNA was detected in 67% of atheromatous plaques (cases) vs. 12% of pudendal arteries (controls) (p = 0.0001). No C. pneumoniae DNA and LPS was detected in PBLCs and biopsic samples, respectively; and no C. pneumoniae strain could be recovered by cell culture from cases. CONCLUSIONS On the basis of our results, PAOD is significantly associated with C. pneumoniae infection through the detection of anti-EB IgG from serum and bacterial DNA from arterial biopsy.
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Affiliation(s)
- José Gutiérrez
- Departamento de Microbiología, Universidad de Granada, Granada, Spain.
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Blanc P, Corsi AM, Gabbuti A, Peduzzi C, Meacci F, Olivieri F, Lauretani F, Francesco M, Ferrucci L. Chlamydia Pneumoniae Seropositivity and Cardiovascular Risk Factors: The InCHIANTI Study. J Am Geriatr Soc 2004; 52:1626-31. [PMID: 15450037 DOI: 10.1111/j.1532-5415.2004.52453.x] [Citation(s) in RCA: 15] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/05/2023]
Abstract
OBJECTIVES To assess the prevalence of Chlamydia pneumoniae (CP) seropositivity and test the hypothesis that CP infection (CPI) is associated with cardiovascular (CV) risk factors and levels of inflammatory biomarkers. DESIGN Cross-sectional survey. SETTING Representative sample of the residents of Greve in Chianti and Bagno a Ripoli, two small towns located in the Chianti geographic area (Tuscany, Italy). PARTICIPANTS A total of 1,304 (age-range: 20-103, 79% aged> or =65) participants of the InCHIANTI study. MEASUREMENTS CP seropositivity was assessed using immunofluorescence. Previous CPI was defined as immunoglobulin (Ig) G > or =1/16 and <1/256, and recent CPI was defined as IgG > or =1/512 or IgM > or =1/16. Inflammatory markers included interleukin (IL)-6, soluble IL-6 receptor (sIL-6r), tumor necrosis factor-alpha (TNF-alpha), IL-1beta, IL-1 receptor antagonist (IL-1ra), iron, ferritin, and C-reactive protein (CRP). CV risk factors included smoking, body mass index (BMI), lipid profile, and hypertension. RESULTS The prevalence of CP seropositivity was 75%, increased with age, and was higher in men than in women (P<.01). CPI was not associated with IL-1beta, IL-1ra, iron, ferritin, CRP, BMI, lipids, and smoking. After adjusting for age and sex, previous or recent CPI was associated with higher TNF-alpha (P<.01), IL-6 (P<.03), sIL-6R (P<.01), and hypertension (P<.02). In additional age and sex-adjusted models, the associations between CPI and TNF-alpha, IL-6, sIL-6r, and hypertension appeared to be mutually independent. CONCLUSION CP seropositivity is highly prevalent in the older population and is a significant, independent correlate of hypertension and circulating levels of TNF-alpha, IL-6, and sIL-6r.
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Affiliation(s)
- Pierluigi Blanc
- Infectious Diseases Section, Hospital SS Annunziata, Florence, Italy
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Rupp J, Berger M, Reiling N, Gieffers J, Lindschau C, Haller H, Dalhoff K, Maass M. Cox-2 inhibition abrogates Chlamydia pneumoniae-induced PGE2 and MMP-1 expression. Biochem Biophys Res Commun 2004; 320:738-44. [PMID: 15240110 DOI: 10.1016/j.bbrc.2004.05.210] [Citation(s) in RCA: 17] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/21/2004] [Indexed: 11/19/2022]
Abstract
Peripheral blood monocytes (PBMC) promote vascular inflammation and atherosclerosis. Chlamydia pneumoniae (Cp) infection of PBMC is found in atherosclerotic patients, appears refractory to antibiotics, and may predispose to vascular damage. In Cp-infected human PBMC we analyzed the role of cyclooxygenase-2 (Cox-2) for the proatherosclerotic key mediators prostaglandin E2 (PGE2) and interstitial collagenase (MMP-1). Cp infection resulted in rapid and sustained Cox-2 mRNA and protein stimulation depending on p38 and p44/42 MAPkinases. Subsequent upregulation of PGE synthase and MMP-1 was completely abrogated by the selective Cox-2 inhibitor NS398. Enhanced synthesis of PGE2 and MMP-1 in Cp infected PBMC is mediated through initiation of the p38 and p44/42 MAPK pathways and requires sustained Cox-2 activation. Selective Cox-2 inhibitors, currently under investigation for cardiovascular risk reduction, may represent a novel therapeutic option for patients with endovascular Cp infection as they target the actuated pathological signal transduction cascade in persistently infected PBMC.
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Affiliation(s)
- Jan Rupp
- Institute of Medical Microbiology and Hygiene, University of Luebeck, Germany
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36
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Linares-Palomino JP, Gutiérrez J, Lopez-Espada C, de Dios Luna J, Ros E, Maroto C. Genomic, serologic, and clinical case-control study of Chlamydia pneumoniae and peripheral artery occlusive disease. J Vasc Surg 2004; 40:359-66. [PMID: 15297834 DOI: 10.1016/j.jvs.2004.04.027] [Citation(s) in RCA: 11] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 10/26/2022]
Abstract
OBJECTIVES Chlamydia pneumoniae has been related to atherosclerotic disease in both seroepidemiologic and genomic studies. We performed a case-control study to determine seropositivity and DNA detection in arteries of patients with peripheral artery occlusive disease and of healthy subjects. METHODS The study included 64 patients with peripheral artery occlusive disease, and 50 control subjects who underwent varicose vein surgery, matched to the patient group for age, sex, and tobacco use. The fibrinogen level in all study subjects was measured as a marker of inflammation. Blood samples were taken from all subjects for determination of immunoglobulin (Ig) G elementary bodies (EB) against C pneumoniae with microimmunofluorescence (MIF) and enzyme-linked immunosorbent assay (ELISA), and of IgA EB with ELISA. The cutoff titers were 1:32 for MIF and 1.1 for ELISA. Biopsy specimens of arterial atheromatous plaque were obtained from patients, and of pudendal artery and saphenous vein from control subjects, and were studied with hemi-nested polymerase chain reaction. RESULTS There were no differences in fibrinogen level between patients and controls. The prevalence of IgG anti-EB with MIF was 78% in patients and 24% in control subjects (P =.0001; odds ratio [OR], 11.3; 95% confidence interval [CI], 4.7-27.2). Prevalence of IgG anti-EB with ELISA was 75% in patients and 16% in control subjects (P =.0001; OR, 15.7; 95% CI, 6.1-40). There were no differences in IgA anti-EB titers. Bacterial DNA was detected in 67% of atheromatous plaques versus 12% of pudendal arteries (P =.0001) and 4% of saphenous veins. A weak correlation was found between seropositivity and the presence of intravascular DNA. CONCLUSIONS Our results support the hypothesis that C pneumoniae is related to the pathogenesis of atherosclerotic peripheral artery occlusive disease. CLINICAL RELEVANCE This study explored the infectious hypothesis in the context of the pathogenesis of atherosclerosis. This hypothesis has been supported by findings that certain infectious agents can cause or accelerate the course of diseases in which the possibility of a microbial cause was not previously proposed, as in the case of peptic ulcer and spongiform encephalopathy. The present study demonstrated the presence of Chlamydia pneumoniae and seropositivity in atheromatous plaques in patients with peripheral artery occlusive disease. These results contribute to a body of research that is opening up the possibility of treating atherosclerotic disease with antibiotic agents, and preventing it with immunization.
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Ferreri AJM, Guidoboni M, Ponzoni M, De Conciliis C, Dell'Oro S, Fleischhauer K, Caggiari L, Lettini AA, Dal Cin E, Ieri R, Freschi M, Villa E, Boiocchi M, Dolcetti R. Evidence for an association between Chlamydia psittaci and ocular adnexal lymphomas. J Natl Cancer Inst 2004; 96:586-94. [PMID: 15100336 DOI: 10.1093/jnci/djh102] [Citation(s) in RCA: 373] [Impact Index Per Article: 17.8] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/27/2022] Open
Abstract
BACKGROUND Ocular adnexal lymphomas may be antigen-driven disorders; however, the source of the putative antigen or antigens is still unknown. Hence, we assessed whether Chlamydiae infection is associated with the development of ocular adnexal lymphomas. METHODS The presence of Chlamydia psittaci, trachomatis, and pneumoniae DNA was investigated by polymerase chain reaction in 40 ocular adnexal lymphoma samples, 20 nonneoplastic orbital biopsies, 26 reactive lymphadenopathy samples, and peripheral blood mononuclear cells (PBMCs) from 21 lymphoma patients and 38 healthy individuals. Seven patients with chlamydia-positive PBMCs were treated with the antibiotic doxycycline, and objective response was assessed in four patients with measurable lymphoma lesions. Differences in Chlamydiae DNA detection between the case patients and the control subjects were analyzed using the Fisher exact test. All statistical tests were two-sided. RESULTS Thirty-two of the 40 (80%) ocular adnexal lymphoma samples carried C. psittaci DNA, whereas all lymphoma samples were negative for C. trachomatis and C. pneumoniae. In contrast, none of the 20 nonneoplastic orbital biopsies (0% versus 80%; P<.001) and only three of 26 (12%) reactive lymphadenopathy samples (12% versus 80%; P<.001) carried the C. psittaci DNA. Nine of 21 (43%) patients with chlamydia-positive lymphomas carried C. psittaci DNA in their PBMCs, whereas none (0%) of the healthy PBMC donors carried C. psittaci DNA in their PBMCs (43% versus 0%; P<.001). One month after doxycycline treatment, chlamydial DNA was no longer detectable in the PBMCs of all seven treated patients, and objective response was observed in two of the four evaluable patients. CONCLUSION Patients with ocular adnexal lymphoma had a high prevalence of C. psittaci infection in both tumor tissue and PBMCs. Persistent C. psittaci infection may contribute to the development of these lymphomas, as was also supported by the clinical responses observed in this study with C. psittaci-eradicating antibiotic therapy.
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Affiliation(s)
- Andrés J M Ferreri
- Department of Radiochemotherapy, San Raffaele H Scientific Institute, Milan, Italy.
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Gelfand EV, Cannon CP. Antibiotics for secondary prevention of coronary artery disease: an ACES hypothesis but we need to PROVE IT. Am Heart J 2004; 147:202-9. [PMID: 14760314 DOI: 10.1016/j.ahj.2003.09.011] [Citation(s) in RCA: 17] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 11/27/2022]
Affiliation(s)
- Eli V Gelfand
- Cardiovascular Division, Beth Israel Deaconess Medical Center, Boston, Mass, USA
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Zebrack JS, Anderson JL. The role of infection in the pathogenesis of cardiovascular disease. PROGRESS IN CARDIOVASCULAR NURSING 2003; 18:42-9. [PMID: 12624571 DOI: 10.1111/j.0889-7204.2003.01421.x] [Citation(s) in RCA: 8] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 11/29/2022]
Abstract
Atherosclerosis is a complex, multifactorial disease. Recently, research has intensified to identify the role of various infections in the pathogenesis of atherosclerosis. Specific agents have been proposed as direct initiators or accelerators of atherosclerosis, while other infectious agents have been proposed as accelerators of atherosclerosis through nonspecific stimulation of the inflammatory cascade. Recently, the total pathogen burden concept has suggested that while each specific infection contributes only slightly to the pathogenesis of atherosclerosis, the cumulative effects of infectious agents contribute greatly. Several randomized trials evaluating antibiotic therapy in the prevention of cardiovascular events have now been completed, although results have been conflicting. This manuscript summarizes current understanding of the role of infectious agents as a trigger of inflammation, as a contributor to atherosclerosis, and the potential role of antibiotic therapy in the treatment of atherosclerosis.
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Affiliation(s)
- James S Zebrack
- Department of Internal Medicine, Division of Cardiology, University of Utah School of Medicine, c/o LDS Hospital, Eighth Avenue and C Street, Salt Lake City, UT 84143, USA.
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Sessa R, Di Pietro M, Schiavoni G, Santino I, Benedetti-Valentini F, Perna R, Romano S, del Piano M. Chlamydia pneumoniae DNA in patients with symptomatic carotid atherosclerotic disease. J Vasc Surg 2003; 37:1027-31. [PMID: 12756349 DOI: 10.1067/mva.2003.200] [Citation(s) in RCA: 44] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/24/2022]
Abstract
OBJECTIVE We evaluated the correlation between the presence of Chlamydia pneumoniae in atherosclerotic carotid plaques, lymph nodes, and peripheral blood mononuclear cells (PBMCs), and symptomatic carotid atherosclerotic disease. METHODS Fifty-one consecutive patients undergoing carotid endarterectomy were enrolled; 18 of the 51 patients had symptomatic disease, whereas 33 had asymptomatic disease. Detection of C pneumoniae DNA in atherosclerotic carotid plaques, lymph nodes, and PBMCs was performed with polymerase chain reaction (PCR). C pneumoniae antibodies were measured with a microimmunofluorescence test. RESULTS C pneumoniae DNA in atherosclerotic carotid plaques was detected in 44.4% of patients with symptomatic disease and in 30.3% of those with asymptomatic disease (P =.48). C pneumoniae DNA in lymph nodes was detected in 33.3% of patients with symptomatic disease and 18.2% of those with asymptomatic disease (P =.19). Prevalence of C pneumoniae DNA in PBMCs was significantly higher in patients with symptomatic disease (72.2%) compared with those with asymptomatic disease (30.3%) (P =.01). Serologic results support the association between C pneumoniae DNA in PBMCs and symptomatic carotid atherosclerotic disease, because seropositivity for anti-chlamydial immunoglobulin (Ig) A antibodies was significantly higher in PCR-positive PBMCs in patients with symptomatic disease compared with patients with asymptomatic disease (P =.02). CONCLUSIONS Detection of C pneumoniae in PBMCs shows that C pneumoniae may be associated with symptomatic carotid atherosclerotic disease. Although we believe there is need for standardization of PCR methods and for assessing sensitivity, specificity, and predictive values of the tests, we suggest that presence of C pneumoniae DNA in PBMCs is a valid surrogate marker of risk for endovascular chlamydial infection. Only long-term cohort studies and interventional trials will clarify the etiopathogenic role of C pneumoniae.
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Affiliation(s)
- Rosa Sessa
- Department of Public Health Sciences, La Sapienza University, Roma, Italy.
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Abstract
Parallel with the mounting evidence that atherosclerosis has a major inflammatory component, provoking agents that may initiate and drive this process have been sought. Infectious agents such as Chlamydia pneumoniae have been alleged to be activators of inflammation that may contribute to atherosclerosis and thus coronary artery disease (CAD) and its associated complications. A logical pneumoniae extension of this theory whether treating C pneumoniae infection with antibiotics and/or modulating inflammatory processes can affect CAD and its sequelae. This article discusses the potential role of C pneumoniae in atherosclerosis, its detection, and the rationale for antibiotics. Additionally, it summarizes the current randomized clinical trials of antichlamydial antibiotics in patients with CAD and draws conclusions based on the results.
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Affiliation(s)
- John P Higgins
- Department of Medicine, University of Oklahoma, Tulsa, USA.
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Smieja M, Mahony J, Petrich A, Boman J, Chernesky M. Association of circulating Chlamydia pneumoniae DNA with cardiovascular disease: a systematic review. BMC Infect Dis 2002; 2:21. [PMID: 12359046 PMCID: PMC130041 DOI: 10.1186/1471-2334-2-21] [Citation(s) in RCA: 51] [Impact Index Per Article: 2.2] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/09/2002] [Accepted: 10/01/2002] [Indexed: 01/18/2023] Open
Abstract
BACKGROUND Chlamydia pneumoniae antigens, nucleic acids, or intact organisms have been detected in human atheroma. However, the presence of antibody does not predict subsequent cardiovascular (CV) events. We performed a systematic review to determine whether the detection of C. pneumoniae DNA in peripheral blood mononuclear cells (PBMC) was associated with CV disease. METHODS We sought studies of C. pneumoniae DNA detection in PBMC by polymerase chain reaction (PCR) among patients with CV disease or other clinical conditions. We pooled studies in which CV patients were compared with non-diseased controls. We analyzed differences between studies by meta-regression, to determine which epidemiological and technical characteristics were associated with higher prevalence. RESULTS Eighteen relevant studies were identified. In nine CV studies with control subjects, the prevalence of circulating C. pneumoniae DNA was 252 of 1763 (14.3%) CV patients and 74 of 874 (8.5%) controls, for a pooled odds ratio of 2.03 (95% CI: 1.34, 3.08, P < 0.001). Prevalence was not adjusted for CV risk factors. Current smoking status, season, and age were associated with C. pneumoniae DNA detection. High prevalence (>40%) was found in patients with cardiac, vascular, chronic respiratory, or renal disease, and in blood donors. Substantial differences between studies were identified in methods of sampling, extraction, and PCR targets. CONCLUSIONS C. pneumoniae DNA detection was associated with CV disease in unadjusted case-control studies. However, adjustment for potentially confounding measures such as smoking or season, and standardization of laboratory methods, are needed to confirm this association.
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Affiliation(s)
- Marek Smieja
- Dept. of Pathology and Molecular Medicine, McMaster University, Hamilton ON, Canada
- Dept. of Medicine, McMaster University, Hamilton ON, Canada
| | - James Mahony
- Dept. of Pathology and Molecular Medicine, McMaster University, Hamilton ON, Canada
| | - Astrid Petrich
- Dept. of Pathology and Molecular Medicine, McMaster University, Hamilton ON, Canada
| | - Jens Boman
- Dept. of Virology, Umea University, Umea, Sweden
| | - Max Chernesky
- Dept. of Pathology and Molecular Medicine, McMaster University, Hamilton ON, Canada
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