Microbiota-derived peptide mimics drive lethal inflammatory cardiomyopathy.
Science
; 366(6467): 881-886, 2019 11 15.
Article
de En
| MEDLINE
| ID: mdl-31727837
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.
Texte intégral:
1
Collection:
01-internacional
Base de données:
MEDLINE
Sujet principal:
Peptides
/
Maladies auto-immunes
/
Bacteroides
/
Cardiomyopathie dilatée
/
Beta-Galactosidase
/
Microbiome gastro-intestinal
/
Myocardite
Limites:
Animals
/
Humans
Langue:
En
Journal:
Science
Année:
2019
Type de document:
Article
Pays d'affiliation:
Suisse