Myocardial gene and protein expression profiles after autoimmune injury in Chagas' disease cardiomyopathy.
One third of the 16 million of individuals infected by the protozoan Trypanosoma cruzi in Latin America eventually develop chronic Chagas' disease cardiomyopathy (CCC), an inflammatory dilated cardiomyopathy with shorter survival than non-inflammatory cardiomyopathies. The presence of a T cell-rich mononuclear inflammatory infiltrate and the relative scarcity of parasites in the heart suggested that chronic inflammation secondary to the autoimmune recognition of cardiac proteins could be a major pathogenetic mechanism. Sera from CCC patients crossreactively recognize cardiac myosin and T. cruzi protein B13. T cell clones elicited from peripheral blood with T. cruzi B13 protein or its peptides could crossreactively recognize epitopes from cardiac myosin heavy chain. Likewise, CD4+ T cell clones infiltrating CCC myocardium crossreactively recognize cardiac myosin and T. cruzi protein B13, and intralesional T cell lines produce the inflammatory cytokines IFN-γ and TNF-α. Conversely, IFN-γ-induced genes and chemokines were found to be upregulated in CCC heart samples, and IFN-γ is able to induce cardiomyocyte expression of atrial natriuretic factor, a key member of the hypertrophy/heart failure signature. Proteomic analysis of CCC heart tissue showed reduced expression of the energy metabolism enzymes. It can be hypothesized that cytokine-induced modulation of cardiomyocyte gene/protein expression may be a novel disease mechanism in CCC, in addition to direct inflammatory damage.
Cunha-Neto
Edecio
E
Laboratory of Immunology, Heart Institute (InCor), University of São Paulo School of Medicine, São Paulo, Brazil. edecunha@usp.br
Teixeira
Priscila C
PC
Fonseca
Simone G
SG
Bilate
Angelina M
AM
Kalil
Jorge
J
D000818:Animals; D000913:Antibodies, Protozoan / Q000276:immunology* / Q000378:metabolism; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology / Q000378:metabolism; D024722:Cardiac Myosins / Q000276:immunology* / Q000378:metabolism; D002598:Chagas Cardiomyopathy / Q000276:immunology* / Q000378:metabolism / Q000469:parasitology; D018925:Chemokines / Q000096:biosynthesis / Q000276:immunology; D003429:Cross Reactions / Q000276:immunology; D000939:Epitopes / Q000276:immunology / Q000378:metabolism; D005786:Gene Expression Regulation / Q000276:immunology*; D006801:Humans; D007371:Interferon-gamma / Q000096:biosynthesis / Q000276:immunology; D009206:Myocardium / Q000276:immunology* / Q000378:metabolism; D015800:Protozoan Proteins / Q000276:immunology* / Q000378:metabolism; D014349:Trypanosoma cruzi / Q000276:immunology* / Q000378:metabolism; D014409:Tumor Necrosis Factor-alpha / Q000096:biosynthesis / Q000276:immunology
D000913:Antibodies, Protozoan; D018925:Chemokines; D000939:Epitopes; D015800:Protozoan Proteins; D014409:Tumor Necrosis Factor-alpha; D007371:Interferon-gamma; D024722:Cardiac Myosins