Microbiota-derived peptide mimics drive lethal inflammatory cardiomyopathy

Myocarditis can develop into inflammatory cardiomyopathy through chronic stimulation of myosin heavy chain 6–specific T helper (TH)1 and TH17 cells. However, mechanisms governing the cardiotoxicity programming of heart-specific T cells have remained elusive. Using a mouse model of spontaneous autoimmune myocarditis, we show that progression of myocarditis to lethal heart disease depends on cardiac myosin–specific TH17 cells imprinted in the intestine by a commensal Bacteroides species peptide mimic. Both the successful prevention of lethal disease in mice by antibiotic therapy and the significantly elevated Bacteroides-specific CD4+ T cell and B cell responses observed in human myocarditis patients suggest that mimic peptides from commensal bacteria can promote inflammatory cardiomyopathy in genetically susceptible individuals. The ability to restrain cardiotoxic T cells through manipulation of the microbiome thereby transforms inflammatory cardiomyopathy into a targetable disease.

Source: ScienceNOW - November 13, 2019 Category: Science Authors: Gil-Cruz, C., Perez-Shibayama, C., De Martin, A., Ronchi, F., van der Borght, K., Niederer, R., Onder, L., Lütge, M., Novkovic, M., Nindl, V., Ramos, G., Arnoldini, M., Slack, E. M. C., Boivin-Jahns, V., Jahns, R., Wyss, M., Mooser, C., Lambrecht, Tags: Immunology, Medicine, Diseases reports Source Type: news