Chlamydia Infections and Heart Disease Linked Through Antigenic Mimicry

Abstract

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.

Molecular Mimicry of an HLA-B27-derived Ligand of Arthritis-linked Subtypes with Chlamydial Proteins

“…If so, chronic stimulation of bacteriaspecific CTL in these individuals could lead to autoimmunity directed against the B27-derived peptide. It is worth noting that a chlamydial peptide homologous to a heart muscle-specific protein induced autoimmune inflammatory heart disease in mice, linking autoimmunity and Chlamydia infection through molecular and antigenic mimicry (66).…”

CD11b+ Monocytes Abrogate Th17 CD4+ T Cell-Mediated Experimental Autoimmune Myocarditis

“…EAM is a CD4 ϩ T cell-mediated disease (19). Nevertheless, adoptive transfer of in vitro restimulated CD4 ϩ T cells isolated from diseased mice usually results in low disease scores in SCID, RAG2 Ϫ/Ϫ , or LPS pretreated wild-type recipients (20,21).…”

Chlamydia pneumoniae in atherosclerosis

“…This peptide, when inoculated into mice, induced vasculitis, fibrosis and thromboses [58]. This mimicry, which is stronger with C. trachomatis than C. pneumoniae does not seem to be the final solution to the association of C. pneumoniae with the chronic process of atherosclerosis.…”

“…steine-rich outer membrane protein Omp2 has a peptide sequence which cross-reacts with a-myosin of heart muscle [58]. This peptide, when inoculated into mice, induced vasculitis, fibrosis and thromboses [58].…”