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Publication

Microbiota-derived peptide mimics drive lethal inflammatory cardiomyopathy

Journal Contribution - Journal Article

Myocarditis can develop into inflammatory cardiomyopathy through chronic stimulation of myosin heavy chain 6-specific T helper (T-H)1 and T(H)17 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 T(H)17 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.
Journal: SCIENCE
ISSN: 1095-9203
Issue: 6467
Volume: 366
Pages: 881 - 886
Publication year:2019
BOF-keylabel:yes
IOF-keylabel:yes
BOF-publication weight:10
CSS-citation score:1
Authors:International
Authors from:Higher Education
Accessibility:Closed