Microbiota-derived peptide mimics drive lethal inflammatory cardiomyopathy
Journal Paper/Review - Nov 15, 2019
Gil Cruz Cristina, Perez Shibayama Christian, De Martin Angelina, Ronchi Francesca, Van der Borght Katrien, Niederer Rebekka, Onder Lucas, Lütge Mechthild, Novkovic Mario, Nindl Veronika, Ramos Gustavo, Arnoldini Markus, Slack Emma M C, Boivin-Jahns Valérie, Jahns Roland, Wyss Madeleine, Mooser Catherine, Lambrecht Bart N, Maeder Micha T., Rickli Hans, Flatz Lukas, Eriksson Urs, Geuking Markus B, McCoy Kathy D, Ludewig Burkhard
Link to Reprint: http://science.sciencemag.org/cgi/rapidpdf/366/6467/881?ijkey=prWyn9fm3ctEE&keytype=ref&siteid=sci
Myocarditis can develop into inflammatory cardiomyopathy through chronic stimulation of myosin heavy chain 6-specific T helper (T)1 and T17 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 T17 cells imprinted in the intestine by a commensal species peptide mimic. Both the successful prevention of lethal disease in mice by antibiotic therapy and the significantly elevated 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.