Note to users. If you're seeing this message, it means that your browser cannot find this page's style/presentation instructions -- or possibly that you are using a browser that does not support current Web standards. Find out more about why this message is appearing, and what you can do to make your experience of our site the best it can be.

Site Tools

  • AAAS
  • Subscribe
  • Feedback

Site Search

Search Advanced

Science 26 February 1999:
Vol. 283. no. 5406, pp. 1335 - 1339
DOI: 10.1126/science.283.5406.1335
Prev | Table of Contents | Next

Reports

Chlamydia Infections and Heart Disease Linked Through Antigenic Mimicry

Kurt Bachmaier, 12 Nikolaus Neu, 3 Luis M. de la Maza, 4 Sukumar Pal, 4 Andrew Hessel, 1 Josef M. Penninger 12*

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 Amgen Institute, Ontario Cancer Institute,
2 Departments of Medical Biophysics and Immunology, University of Toronto, Toronto, Ontario M5G 2C1, Canada.
3 Department of Pediatrics, University of Innsbruck, Medical School, Innsbruck A-6020, Austria.
4 Department of Pathology, University of California, Irvine, CA 92697-4800, USA.
*   To whom correspondence should be addressed. E-mail: jpenning{at}amgen.com

Read the Full Text


THIS ARTICLE HAS BEEN CITED BY OTHER ARTICLES:
CD11b+ Monocytes Abrogate Th17 CD4+ T Cell-Mediated Experimental Autoimmune Myocarditis.
A. Valaperti, R. R. Marty, G. Kania, D. Germano, N. Mauermann, S. Dirnhofer, B. Leimenstoll, P. Blyszczuk, C. Dong, C. Mueller, et al. (2008)
J. Immunol. 180, 2686-2695
   Abstract »    Full Text »    PDF »
Identification of Endogenously Presented Peptides from Chlamydia trachomatis with High Homology to Human Proteins and to a Natural Self-ligand of HLA-B27.
J. J. Cragnolini and J. A. L. de Castro (2008)
Mol. Cell. Proteomics 7, 170-180
   Abstract »    Full Text »    PDF »
Dual T Cell Receptor Expressing CD8+ T Cells with Tumor- and Self-Specificity Can Inhibit Tumor Growth without Causing Severe Autoimmunity.
M. Weinhold, D. Sommermeyer, W. Uckert, and T. Blankenstein (2007)
J. Immunol. 179, 5534-5542
   Abstract »    Full Text »    PDF »
Persistent Chlamydia pneumoniae Infection of Cardiomyocytes Is Correlated with Fatal Myocardial Infarction.
L. G. Spagnoli, S. Pucci, E. Bonanno, A. Cassone, F. Sesti, A. Ciervo, and A. Mauriello (2007)
Am. J. Pathol. 170, 33-42
   Abstract »    Full Text »    PDF »
T-bet negatively regulates autoimmune myocarditis by suppressing local production of interleukin 17.
M. Rangachari, N. Mauermann, R. R. Marty, S. Dirnhofer, M. O. Kurrer, V. Komnenovic, J. M. Penninger, and U. Eriksson (2006)
J. Exp. Med. 203, 2009-2019
   Abstract »    Full Text »    PDF »
Molecular mimicry revisited: gut bacteria and multiple sclerosis..
F. C. Westall (2006)
J. Clin. Microbiol. 44, 2099-2104
   Abstract »    Full Text »    PDF »
T Cell Epitope Mimicry in Antiglomerular Basement Membrane Disease.
J. Arends, J. Wu, J. Borillo, L. Troung, C. Zhou, N. Vigneswaran, and Y.-H. Lou (2006)
J. Immunol. 176, 1252-1258
   Abstract »    Full Text »    PDF »
Splenic PGE2-releasing macrophages regulate Th1 and Th2 immune responses in mice treated with heat-killed BCG.
Y. Shibata, R. A. Henriksen, I. Honda, R. M. Nakamura, and Q. N. Myrvik (2005)
J. Leukoc. Biol. 78, 1281-1290
   Abstract »    Full Text »    PDF »
T Cell Mimicry and Epitope Specificity of Cross-Reactive T Cell Clones from Rheumatic Heart Disease.
N. M. J. Ellis, Y. Li, W. Hildebrand, V. A. Fischetti, and M. W. Cunningham (2005)
J. Immunol. 175, 5448-5456
   Abstract »    Full Text »    PDF »
A Structural Basis for CD8+ T Cell-dependent Recognition of Non-homologous Peptide Ligands: IMPLICATIONS FOR MOLECULAR MIMICRY IN AUTOREACTIVITY.
T. Sandalova, J. Michaelsson, R. A. Harris, J. Odeberg, G. Schneider, K. Karre, and A. Achour (2005)
J. Biol. Chem. 280, 27069-27075
   Abstract »    Full Text »    PDF »
CD8+ T cells specific for a potential HLA-A*0201 epitope from Chlamydophila pneumoniae are present in the PBMCs from infected patients.
J.-P. Carralot, C. Dumrese, R. Wessel, R. Riessen, I. Autenrieth, S. Walter, O. Schoor, S. Stevanovic, H.-G. Rammensee, and S. Pascolo (2005)
Int. Immunol. 17, 591-597
   Abstract »    Full Text »    PDF »
A CD8+ T Cell Heptaepitope Minigene Vaccine Induces Protective Immunity against Chlamydia pneumoniae.
I. Pinchuk, B. C. Starcher, B. Livingston, A. Tvninnereim, S. Wu, E. Appella, J. Sidney, A. Sette, and B. Wizel (2005)
J. Immunol. 174, 5729-5739
   Abstract »    Full Text »    PDF »
Chlamydia pneumoniae infections in mouse models: relevance for atherosclerosis research.
M. D. de Kruif, E. C.M. van Gorp, T. T. Keller, J. M. Ossewaarde, and H. ten Cate (2005)
Cardiovasc Res 65, 317-327
   Abstract »    Full Text »    PDF »
Viral Delivery of an Epitope from Haemophilus influenzae Induces Central Nervous System Autoimmune Disease by Molecular Mimicry.
J. L. Croxford, H. A. Anger, and S. D. Miller (2005)
J. Immunol. 174, 907-917
   Abstract »    Full Text »    PDF »
Peptides From Common Viral and Bacterial Pathogens Can Efficiently Activate Diabetogenic T-Cells.
V. A. Judkowski, G. M. Allicotti, N. Sarvetnick, and C. Pinilla (2004)
Diabetes 53, 2301-2309
   Abstract »    Full Text »    PDF »
A Novel Recombinant Multisubunit Vaccine against Chlamydia.
F. O. Eko, Q. He, T. Brown, L. McMillan, G. O. Ifere, G. A. Ananaba, D. Lyn, W. Lubitz, K. L. Kellar, C. M. Black, et al. (2004)
J. Immunol. 173, 3375-3382
   Abstract »    Full Text »    PDF »
Widespread Myocardial Inflammation and Infarct-Related Artery Patency.
A. Abbate, E. Bonanno, A. Mauriello, R. Bussani, G. G.L. Biondi-Zoccai, G. Liuzzo, A. M. Leone, F. Silvestri, A. Dobrina, F. Baldi, et al. (2004)
Circulation 110, 46-50
   Abstract »    Full Text »    PDF »
In Vivo Cyclophosphamide and IL-2 Treatment Impedes Self-Antigen-Induced Effector CD4 Cell Tolerization: Implications for Adoptive Immunotherapy.
M. A. Mihalyo, A. D. H. Doody, J. P. McAleer, E. C. Nowak, M. Long, Y. Yang, and A. J. Adler (2004)
J. Immunol. 172, 5338-5345
   Abstract »    Full Text »    PDF »
A Spontaneous Model for Autoimmune Myocarditis Using the Human MHC Molecule HLA-DQ8.
J. A. Taylor, E. Havari, M. F. McInerney, R. Bronson, K. W. Wucherpfennig, and M. A. Lipes (2004)
J. Immunol. 172, 2651-2658
   Abstract »    Full Text »    PDF »
Autoimmune cardiomyopathy and heart block develop spontaneously in HLA-DQ8 transgenic IA{beta} knockout NOD mice.
J. F. Elliott, J. Liu, Z.-N. Yuan, N. Bautista-Lopez, S. L. Wallbank, K. Suzuki, D. Rayner, P. Nation, M. A. Robertson, G. Liu, et al. (2003)
PNAS 100, 13447-13452
   Abstract »    Full Text »    PDF »
CpG-Containing Oligodeoxynucleotide 1826 Converts the Weak Uveitogenic Rat Interphotoreceptor Retinoid-Binding Protein Peptide 1181-1191 into a Strong Uveitogen.
H. Shao, S. Lei, S. L. Sun, J. Xiang, H. J. Kaplan, and D. Sun (2003)
J. Immunol. 171, 4780-4785
   Abstract »    Full Text »    PDF »
Molecular Mimicry between Helicobacter pylori Antigens and H+,K+-Adenosine Triphosphatase in Human Gastric Autoimmunity.
A. Amedei, M. P. Bergman, B. J. Appelmelk, A. Azzurri, M. Benagiano, C. Tamburini, R. van der Zee, J. L. Telford, C. M.J.E. Vandenbroucke-Grauls, M. M. D'Elios, et al. (2003)
J. Exp. Med. 198, 1147-1156
   Abstract »    Full Text »    PDF »
T helper type 1 lymphocytes drive inflammation in human atherosclerotic lesions.
M. Benagiano, A. Azzurri, A. Ciervo, A. Amedei, C. Tamburini, M. Ferrari, J. L. Telford, C. T. Baldari, S. Romagnani, A. Cassone, et al. (2003)
PNAS 100, 6658-6663
   Abstract »    Full Text »    PDF »
Chlamydia pneumoniae and Coronary Artery Disease: The Antibiotic Trials.
J. P. Higgins (2003)
Mayo Clin. Proc. 78, 321-332
   Abstract »    PDF »
Activation of Dendritic Cells through the Interleukin 1 Receptor 1 Is Critical for the Induction of Autoimmune Myocarditis.
U. Eriksson, M. O. Kurrer, I. Sonderegger, G. Iezzi, A. Tafuri, L. Hunziker, S. Suzuki, K. Bachmaier, R. M. Bingisser, J. M. Penninger, et al. (2003)
J. Exp. Med. 197, 323-331
   Abstract »    Full Text »    PDF »
Infection, Inflammation, and Atherosclerosis.
J. D. Spence and J. Norris (2003)
Stroke 34, 333-334
   Full Text »    PDF »
Chlamydia pneumoniae Infection of the Central Nervous System Worsens Experimental Allergic Encephalitis.
C. Du, S.-Y. Yao, A. Ljunggren-Rose, and S. Sriram (2002)
J. Exp. Med. 196, 1639-1644
   Abstract »    Full Text »    PDF »
Infection of myocytes with chlamydiae.
G. Wang, F. Burczynski, B. Hasinoff, and G. Zhong (2002)
Microbiology 148, 3955-3959
   Abstract »    Full Text »    PDF »
Chlamydophila pneumoniae (Chlamydia pneumoniae) accelerates the formation of complex atherosclerotic lesions in Apo E3-Leiden mice.
R Ezzahiri, H.J.M.G Nelissen-Vrancken, H.A.J.M Kurvers, F.R.M Stassen, I Vliegen, G.E.L.M Grauls, M.M.L van Pul, P.J.E.H.M Kitslaar, and C.A Bruggeman (2002)
Cardiovasc Res 56, 269-276
   Abstract »    Full Text »    PDF »
Molecular Mimicry of an HLA-B27-derived Ligand of Arthritis-linked Subtypes with Chlamydial Proteins.
M. Ramos, I. Alvarez, L. Sesma, A. Logean, D. Rognan, and J. A. Lopez de Castro (2002)
J. Biol. Chem. 277, 37573-37581
   Abstract »    Full Text »    PDF »
Functional Activation of Myelin-Specific T Cells by Virus-Induced Molecular Mimicry.
J. K. Olson, T. N. Eagar, and S. D. Miller (2002)
J. Immunol. 169, 2719-2726
   Abstract »    Full Text »    PDF »
Bystander CD8 T Cell-Mediated Demyelination After Viral Infection of the Central Nervous System.
J. S. Haring, L. L. Pewe, and S. Perlman (2002)
J. Immunol. 169, 1550-1555
   Abstract »    Full Text »    PDF »
Memorizing innate instructions requires a sufficiently specific adaptive immune system.
J. A. M. Borghans and R. J. De Boer (2002)
Int. Immunol. 14, 525-532
   Abstract »    Full Text »    PDF »
Antibodies to 60-Kilodalton Heat Shock Protein and Outer Membrane Protein 2 of Chlamydia pneumoniae in Patients with Coronary Heart Disease.
A. Ciervo, P. Visca, A. Petrucca, L. M. Biasucci, A. Maseri, and A. Cassone (2002)
Clin. Vaccine Immunol. 9, 66-74
   Abstract »    Full Text »    PDF »
Induction of Myocarditis and Valvulitis in Lewis Rats by Different Epitopes of Cardiac Myosin and Its Implications in Rheumatic Carditis.
J. E. Galvin, M. E. Hemric, S. D. Kosanke, S. M. Factor, A. Quinn, and M. W. Cunningham (2002)
Am. J. Pathol. 160, 297-306
   Abstract »    Full Text »    PDF »
Dilated cardiomyopathy and Chlamydia pneumoniae infection.
H SONG, H TASAKI, A YASHIRO, K YAMASHITA, T TOYOKAWA, Y NAGAI, H TAKATSU, H TANIGUCHI, and Y NAKASHIMA (2001)
Heart 86, 456-458
   Full Text »    PDF »
Predominant Role of Toll-Like Receptor 2 Versus 4 in Chlamydia pneumoniae-Induced Activation of Dendritic Cells.
S. Prebeck, C. Kirschning, S. Durr, C. da Costa, B. Donath, K. Brand, V. Redecke, H. Wagner, and T. Miethke (2001)
J. Immunol. 167, 3316-3323
   Abstract »    Full Text »    PDF »
A Chlamydia pneumoniae-Specific Peptide Induces Experimental Autoimmune Encephalomyelitis in Rats.
D. C. Lenz, L. Lu, S. B. Conant, N. A. Wolf, H. C. Gerard, J. A. Whittum-Hudson, A. P. Hudson, and R. H. Swanborg (2001)
J. Immunol. 167, 1803-1808
   Abstract »    Full Text »    PDF »
Expansion of the Antigenic Repertoire of a Single T Cell Receptor upon T Cell Activation.
A. Amrani, P. Serra, J. Yamanouchi, J. D. Trudeau, R. Tan, J. F. Elliott, and P. Santamaria (2001)
J. Immunol. 167, 655-666
   Abstract »    Full Text »    PDF »
Functional Evidence That Conserved TCR CDR{{alpha}}3 Loop Docking Governs the Cross-Recognition of Closely Related Peptide:Class I Complexes.
I. Messaoudi, J. LeMaoult, B. M. Metzner, M. J. Miley, D. H. Fremont, and J. Nikolich-Zugich (2001)
J. Immunol. 167, 836-843
   Abstract »    Full Text »    PDF »
Cardiac Myosin and the TH1/TH2 Paradigm in Autoimmune Myocarditis.
M. W. Cunningham (2001)
Am. J. Pathol. 159, 5-12
   Full Text »    PDF »
Chlamydia pneumoniae Infection Does Not Induce or Modify Atherosclerosis in Mice.
G. Caligiuri, M. Rottenberg, A. Nicoletti, H. Wigzell, and G. K. Hansson (2001)
Circulation 103, 2834-2838
   Abstract »    Full Text »    PDF »
Changes in the prevalence of chronic disability in the United States black and nonblack population above age 65 from 1982 to 1999.
K. G. Manton and X. Gu (2001)
PNAS
   Abstract »    Full Text »
Molecular Mimicry in Lyme Arthritis Demonstrated at the Single Cell Level: LFA-1{{alpha}}L Is a Partial Agonist for Outer Surface Protein A-Reactive T Cells.
C. Trollmo, A. L. Meyer, A. C. Steere, D. A. Hafler, and B. T. Huber (2001)
J. Immunol. 166, 5286-5291
   Abstract »    Full Text »    PDF »
Chlamydia pneumoniae Does Not Increase Atherosclerosis in the Aortic Root of Apolipoprotein E-Deficient Mice.
K. Aalto-Setala, K. Laitinen, L. Erkkila, M. Leinonen, M. Jauhiainen, C. Ehnholm, M. Tamminen, M. Puolakkainen, I. Penttila, and P. Saikku (2001)
Arterioscler. Thromb. Vasc. Biol. 21, 578-584
   Abstract »    Full Text »    PDF »
Search for Chlamydia pneumoniae genes and their expression in atherosclerotic plaques of carotid arteries.
M. VALASSINA, L. MIGLIORINI, A. SANSONI, G. SANI, D. CORSARO, M. G. CUSI, P. E. VALENSIN, and C. CELLESI (2001)
J. Med. Microbiol. 50, 228-232
   Abstract »    Full Text »    PDF »
Detection of Helicobacter pylori in Human Carotid Atherosclerotic Plaques Editorial Comment.
S. F. Ameriso, E. A. Fridman, R. C. Leiguarda, G. E. Sevlever, and J. D. Spence (2001)
Stroke 32, 385-391
   Abstract »    Full Text »    PDF »
Lethal Autoimmune Myocarditis in Interferon-{{gamma}} Receptor-Deficient Mice : Enhanced Disease Severity by Impaired Inducible Nitric Oxide Synthase Induction.
U. Eriksson, M. O. Kurrer, R. Bingisser, H. P. Eugster, P. Saremaslani, F. Follath, S. Marsch, and U. Widmer (2001)
Circulation 103, 18-21
   Abstract »    Full Text »    PDF »
Molecular Mimicry in Neurological Diseases.
S. Markovic-Plese (2000)
Neuroscientist 6, 428-432
   Abstract »    PDF »
Bacterial Immunoglobulin Superantigen Proteins A and L Activate Human Heart Mast Cells by Interacting with Immunoglobulin E.
A. Genovese, J.-P. Bouvet, G. Florio, B. Lamparter-Schummert, L. Bjorck, and G. Marone (2000)
Infect. Immun. 68, 5517-5524
   Abstract »    Full Text »    PDF »
GENERAL CARDIOLOGY: Myocarditis, pericarditis and other pericardial diseases.
C. M Oakley (2000)
Heart 84, 449-454
   Full Text »
Peptide Dose, MHC Affinity, and Target Self-Antigen Expression Are Critical for Effective Immunotherapy of Nonobese Diabetic Mouse Prediabetes.
S. Winer, L. Gunaratnam, I. Astsatourov, R. K. Cheung, V. Kubiak, W. Karges, D. Hammond-McKibben, R. Gaedigk, D. Graziano, M. Trucco, et al. (2000)
J. Immunol. 165, 4086-4094
   Abstract »    Full Text »    PDF »
Microorganisms in the aetiology of atherosclerosis.
S A Morre, W Stooker, W K Lagrand, A J C van den Brule, and H W M Niessen (2000)
J. Clin. Pathol. 53, 647-654
   Abstract »    Full Text »    PDF »
Herpesvirus Infection Accelerates Atherosclerosis in the Apolipoprotein E-Deficient Mouse.
D. G. Alber, K. L. Powell, P. Vallance, D. A. Goodwin, and C. Grahame-Clarke (2000)
Circulation 102, 779-785
   Abstract »    Full Text »    PDF »
Infection and Atherosclerosis : Potential Roles of Pathogen Burden and Molecular Mimicry.
S. E. Epstein, J. Zhu, M. S. Burnett, Y. F. Zhou, G. Vercellotti, and D. Hajjar (2000)
Arterioscler. Thromb. Vasc. Biol. 20, 1417-1420
   Abstract »    Full Text »    PDF »
Roles of Interleukin-12 and Gamma Interferon in Murine Chlamydia pneumoniae Infection.
Y. Geng, K. Berencsi, Z. Gyulai, T. Valyi-Nagy, E. Gonczol, and G. Trinchieri (2000)
Infect. Immun. 68, 2245-2253
   Abstract »    Full Text »    PDF »
T Cell-Independent Rescue of B Lymphocytes from Peripheral Immune Tolerance.
V. Kouskoff, G. Lacaud, and D. Nemazee (2000)
Science 287, 2501-2503
   Abstract »    Full Text »
Genome sequences of Chlamydia trachomatis MoPn and Chlamydia pneumoniae AR39.
T. D. Read, R. C. Brunham, C. Shen, S. R. Gill, J. F. Heidelberg, O. White, E. K. Hickey, J. Peterson, T. Utterback, K. Berry, et al. (2000)
Nucleic Acids Res. 28, 1397-1406
   Abstract »    Full Text »    PDF »
Seroreactivity to Chlamydia trachomatis Hsp10 Correlates with Severity of Human Genital Tract Disease.
D. LaVerda, L. N. Albanese, P. E. Ruther, S. G. Morrison, R. P. Morrison, K. A. Ault, and G. I. Byrne (2000)
Infect. Immun. 68, 303-309
   Abstract »    Full Text »    PDF »
Molecular Mimicry and Autoimmunity.
L. J. Albert and R. D. Inman (1999)
N. Engl. J. Med. 341, 2068-2074
   Full Text »    PDF »
Are All Diseases Infectious? Another Look.
B. Lorber (1999)
Ann Intern Med 131, 989-990
   Full Text »
The role of Chlamydia in coronary heart disease--fact or fiction?.
T. Quaschning and C. Wanner (1999)
Nephrol. Dial. Transplant. 14, 2800-2803
   Full Text »    PDF »
Chlamydia trachomatis (Mouse Pneumonitis Strain) Induces Cardiovascular Pathology following Respiratory Tract Infection.
Y. Fan, S. Wang, and X. Yang (1999)
Infect. Immun. 67, 6145-6151
   Abstract »    Full Text »    PDF »
Does Chlamydia pneumoniae Cause Atherosclerosis?.
J. T. Grayston (1999)
Arch Surg 134, 930-934
   Full Text »    PDF »
Drug Treatment of Lipid Disorders.
R. H. Knopp (1999)
N. Engl. J. Med. 341, 498-511
   Full Text »    PDF »
Infection and Atherosclerosis : Emerging Mechanistic Paradigms.
S. E. Epstein, Y. F. Zhou, and J. Zhu (1999)
Circulation 100 , e20-e28
   Abstract »    Full Text »    PDF »
How Specific Should Immunological Memory Be?.
J. A. M. Borghans, A. J. Noest, and R. J. De Boer (1999)
J. Immunol. 163, 569-575
   Abstract »    Full Text »    PDF »
The Search for Unrecognized Pathogens.
D. A. Relman (1999)
Science 284, 1308-1310
   Abstract »    Full Text »
Is There a Molecular Mechanism Linking Chlamydia and Heart Disease?.
(1999)
Journal Watch (General) 1999, 8
   Full Text »
From the Cover: Changes in the prevalence of chronic disability in the United States black and nonblack population above age 65 from 1982 to 1999.
K. G. Manton and X. Gu (2001)
PNAS 98, 6354-6359
   Abstract »    Full Text »    PDF »


To Advertise     Find Products

Science. ISSN 0036-8075 (print), 1095-9203 (online)