Back to Search
Start Over
Microbiota-derived peptide mimics drive lethal inflammatory cardiomyopathy.
- Source :
-
Science (New York, N.Y.) [Science] 2019 Nov 15; Vol. 366 (6467), pp. 881-886. - Publication Year :
- 2019
-
Abstract
- Myocarditis can develop into inflammatory cardiomyopathy through chronic stimulation of myosin heavy chain 6-specific T helper (T <subscript>H</subscript> )1 and T <subscript>H</subscript> 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 <subscript>H</subscript> 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 <superscript>+</superscript> 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.<br /> (Copyright © 2019 The Authors, some rights reserved; exclusive licensee American Association for the Advancement of Science. No claim to original U.S. Government Works.)
- Subjects :
- Animals
Autoimmune Diseases immunology
B-Lymphocytes immunology
CD4-Positive T-Lymphocytes immunology
Disease Models, Animal
Humans
Intestines microbiology
Mice
Mice, Inbred BALB C
Mice, Transgenic
Myocarditis immunology
Myosin Heavy Chains genetics
Myosin Heavy Chains immunology
Th17 Cells immunology
Autoimmune Diseases complications
Bacteroides immunology
Cardiomyopathy, Dilated immunology
Cardiomyopathy, Dilated microbiology
Gastrointestinal Microbiome immunology
Myocarditis complications
Peptides immunology
beta-Galactosidase immunology
Subjects
Details
- Language :
- English
- ISSN :
- 1095-9203
- Volume :
- 366
- Issue :
- 6467
- Database :
- MEDLINE
- Journal :
- Science (New York, N.Y.)
- Publication Type :
- Academic Journal
- Accession number :
- 31727837
- Full Text :
- https://doi.org/10.1126/science.aav3487