Chlamydia infections and heart disease linked through antigenic mimicry.

Chlamydia infections are epidemiologically linked to human heart disease. A peptide from the murine heart muscle-specific alpha myosin heavy chain that has sequence homology to the 60-kilodalton cysteine-rich outer membrane proteins of Chlamydia pneumoniae, C. psittaci, and C. trachomatis was shown to induce autoimmune inflammatory heart disease in mice. Injection of the homologous Chlamydia peptides into mice also induced perivascular inflammation, fibrotic changes, and blood vessel occlusion in the heart, as well as triggering T and B cell reactivity to the homologous endogenous heart muscle-specific peptide. Chlamydia DNA functioned as an adjuvant in the triggering of peptide-induced inflammatory heart disease. Infection with C. trachomatis led to the production of autoantibodies to heart muscle-specific epitopes. Thus, Chlamydia-mediated heart disease is induced by antigenic mimicry of a heart muscle-specific protein.

[1]  J. Carlquist,et al.  Infection with Chlamydia pneumoniae accelerates the development of atherosclerosis and treatment with azithromycin prevents it in a rabbit model. , 1998, Circulation.

[2]  T. Mak,et al.  Induction of autoimmunity in the absence of CD28 costimulation. , 1996, Journal of immunology.

[3]  Y. Goo,et al.  Chlamydia pneumoniae (TWAR) in coronary arteries of young adults (15-34 years old). , 1995, Proceedings of the National Academy of Sciences of the United States of America.

[4]  E. Feskens,et al.  Chlamydia pneumoniae is a risk factor for coronary heart disease in symptom-free elderly men, but Helicobacter pylori and cytomegalovirus are not , 1998, Epidemiology and Infection.

[5]  T. Stokes,et al.  Screening for Chlamydia in general practice: a literature review and summary of the evidence. , 1997, Journal of public health medicine.

[6]  I. Clarke,et al.  The nucleotide sequence of the 60 kDa cysteine rich outer membrane protein of Chlamydia psittaci strain EAE/A22/M. , 1990, Nucleic acids research.

[7]  T. Fielder,et al.  Sequence diversity of the 60-kilodalton protein and of a putative 15-kilodalton protein between the trachoma and lymphogranuloma venereum biovars of Chlamydia trachomatis , 1991, Infection and immunity.

[8]  D. Patton,et al.  Experimental rabbit models of Chlamydia pneumoniae infection. , 1996, The American journal of pathology.

[9]  M. Oldstone,et al.  Virus-induced autoimmune disease , 1996, Current Opinion in Immunology.

[10]  A. Camm,et al.  Elevated Chlamydia pneumoniae Antibodies, Cardiovascular Events, and Azithromycin in Male Survivors of Myocardial Infarction , 1997 .

[11]  J. Bach,et al.  Insulin-dependent diabetes mellitus as an autoimmune disease. , 1994, Endocrine reviews.

[12]  L. Campbell,et al.  Murine models of Chlamydia pneumoniae infection and atherosclerosis. , 1997, The Journal of infectious diseases.

[13]  J. Friedman,et al.  The role of heart binding antibodies in rheumatic fever. , 1983, Advances in experimental medicine and biology.

[14]  M. Laakso,et al.  Association of Chlamydia pneumoniae and acute coronary heart disease events in non-insulin dependent diabetic and non-diabetic subjects in Finland. , 1996, European heart journal.

[15]  K. Beisel,et al.  Myocarditis-inducing epitope of myosin binds constitutively and stably to I-Ak on antigen-presenting cells in the heart , 1995, The Journal of experimental medicine.

[16]  J. Ramirez,et al.  Replication of Chlamydia pneumoniae in vitro in human macrophages, endothelial cells, and aortic artery smooth muscle cells , 1996, Infection and immunity.

[17]  J. Collazos,et al.  Myopericarditis due to Chlamydia psittaci. The role of autoimmunity. , 1997, Scandinavian journal of infectious diseases.

[18]  E. Peterson,et al.  Immunization with an acellular vaccine consisting of the outer membrane complex of Chlamydia trachomatis induces protection against a genital challenge , 1997, Infection and immunity.

[19]  H Cantor,et al.  Molecular mimicry by herpes simplex virus-type 1: autoimmune disease after viral infection. , 1998, Science.

[20]  Troy Krahl,et al.  Diabetes induced by Coxsackie virus: Initiation by bystander damage and not molecular mimicry , 1998, Nature Medicine.

[21]  M. Oldstone.  Molecular mimicry and autoimmune disease , 1987, Cell.

[22]  J. Ramírez.  Isolation of Chlamydia pneumoniae from the Coronary Artery of a Patient with Coronary Atherosclerosis , 1996, Annals of Internal Medicine.

[23]  C. Janeway,et al.  A tale of two T cells. , 1998, Immunity.

[24]  G. Dagenais,et al.  Hyperinsulinemia as an independent risk factor for ischemic heart disease. , 1996, The New England journal of medicine.

[25]  T. Quinn,et al.  Epidemiologic and microbiologic correlates of Chlamydia trachomatis infection in sexual partnerships. , 1996, JAMA.

[26]  I. Fong,et al.  Rabbit model for Chlamydia pneumoniae infection , 1997, Journal of clinical microbiology.

[27]  D. Levy,et al.  Prediction of coronary heart disease using risk factor categories. , 1998, Circulation.

[28]  H. Fukushi,et al.  Demonstration of Chlamydia pneumoniae in atherosclerotic lesions of coronary arteries. , 1993, The Journal of infectious diseases.

[29]  M. Nieminen,et al.  SEROLOGICAL EVIDENCE OF AN ASSOCIATION OF A NOVEL CHLAMYDIA, TWAR, WITH CHRONIC CORONARY HEART DISEASE AND ACUTE MYOCARDIAL INFARCTION , 1988, The Lancet.

[30]  T. Mak,et al.  iNOS expression and nitrotyrosine formation in the myocardium in response to inflammation is controlled by the interferon regulatory transcription factor 1. , 1997, Circulation.

[31]  K. Beisel,et al.  Cardiac myosin induces myocarditis in genetically predisposed mice. , 1987, Journal of immunology.

[32]  T. Inagami,et al.  Chimeric mice carrying 'regional' targeted deletion of the angiotensin type 1A receptor gene. Evidence against the role for local angiotensin in the in vivo feedback regulation of renin synthesis in juxtaglomerular cells. , 1996, The Journal of clinical investigation.

[33]  P. Ridker.  Inflammation, infection, and cardiovascular risk: how good is the clinical evidence? , 1998, Circulation.

[34]  M. Maass,et al.  Endovascular Presence of Chlamydia pneumoniae in Patients with Hemodynamically Effective Carotid Artery Stenosis , 1997, Angiology.

[35]  M. Leschke,et al.  Antibodies to cytomegalovirus or Chlamydia pneumoniae and coronary heart disease , 1998, The Lancet.

[36]  E. Worthington,et al.  Chlamydia pneumoniae myocarditis , 1995, The Lancet.

[37]  J. Danesh,et al.  Chronic infections and coronary heart disease: is there a link? , 1997, The Lancet.

[38]  I. Clarke,et al.  Immunoreactivity of the 60 kDa cysteine-rich proteins of Chlamydia trachomatis, Chlamydia psittaci and Chlamydia pneumoniae expressed in Escherichia coli. , 1994, Microbiology.

[39]  A. Coles,et al.  The nucleotide and derived amino acid sequence of the omp2 gene of Chlamydia trachomatis serovar E. , 1990, Nucleic acids research.

[40]  J. Penninger,et al.  Identification of cardiac myosin peptides capable of inducing autoimmune myocarditis in BALB/c mice. , 1996, The Journal of clinical investigation.

[41]  A. Krieg,et al.  CpG DNA is a potent enhancer of specific immunity in mice immunized with recombinant hepatitis B surface antigen. , 1998, Journal of immunology.

[42]  M. Atkinson,et al.  Insulin-dependent diabetes mellitus: the hypothesis of molecular mimicry between islet cell antigens and microorganisms. , 1997, Molecular medicine today.

[43]  U. Mamat,et al.  Endovascular presence of viable Chlamydia pneumoniae is a common phenomenon in coronary artery disease. , 1998, Journal of the American College of Cardiology.

[44]  B. Munoz,et al.  Trachoma: the forgotten cause of blindness. , 1997, Epidemiologic reviews.

[45]  M L Woods,et al.  Increased incidence of Chlamydia species within the coronary arteries of patients with symptomatic atherosclerotic versus other forms of cardiovascular disease. , 1996, Journal of the American College of Cardiology.

[46]  S. Wang,et al.  Childhood myocarditis associated with Chlamydia trachomatis infection. , 1981, JAMA.

[47]  M. Comanducci,et al.  Diversity of the Chlamydia trachomatis common plasmid in biovars with different pathogenicity. , 1990, Plasmid.

[48]  J. Penninger,et al.  Cardiac myosin-induced myocarditis: target recognition by autoreactive T cells requires prior activation of cardiac interstitial cells. , 1996, Laboratory investigation; a journal of technical methods and pathology.

[49]  P. Allen,et al.  Expression of myosin-class II major histocompatibility complexes in the normal myocardium occurs before induction of autoimmune myocarditis. , 1992, Proceedings of the National Academy of Sciences of the United States of America.

[50]  R. Schmidt,et al.  Specificity of detection of Chlamydia pneumoniae in cardiovascular atheroma: evaluation of the innocent bystander hypothesis. , 1997, The American journal of pathology.

[51]  D. Stewart,et al.  Detection of Chlamydia pneumoniae TWAR in human coronary atherectomy tissues. , 1995, The Journal of infectious diseases.

[52]  G. Bishop,et al.  CpG motifs in bacterial DNA trigger direct B-cell activation , 1995, Nature.