Congratulations to IMPACTT Director and Platform 1 Lead Dr. Kathy McCoy, as well as Education & Mentorship Lead Dr. Markus Geuking, on this recent publication!
Abstract
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.
Publication: Microbiota-derived peptide mimics drive lethal inflammatory cardiomyopathy. Gil-Cruz C, Perez-Shibayama C, De Martin A, Ronchi F, Van Der Borght K, Niederer R, Onder L, Lutge M, Novkovic M, Nindl V, Ramos G, Arnoldini M, Slack EM, Boivin-Jahns V, Jahns R, Wyss M, Mooser C, Lambrecht BN, Maeder MT, Rickli H, Flatz L, Eriksson U, Geuking MB, McCoy, KD, Ludewig B. Science. 15 Nov 2019.
