Microbiota-derived peptide mimics drive lethal inflammatory cardiomyopathy.

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; ... (2019). Microbiota-derived peptide mimics drive lethal inflammatory cardiomyopathy. Science, 366(6467), pp. 881-886. American Association for the Advancement of Science 10.1126/science.aav3487

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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.

Item Type:

Journal Article (Original Article)

Division/Institute:

04 Faculty of Medicine > Department of Gastro-intestinal, Liver and Lung Disorders (DMLL) > Clinic of Visceral Surgery and Medicine > Gastroenterology
04 Faculty of Medicine > Pre-clinic Human Medicine > BioMedical Research (DBMR) > DBMR Forschung Mu35 > Forschungsgruppe Gastroenterologie / Mukosale Immunologie
04 Faculty of Medicine > Pre-clinic Human Medicine > BioMedical Research (DBMR) > DBMR Forschung Mu35 > Forschungsgruppe Gastroenterologie / Mukosale Immunologie

UniBE Contributor:

Ronchi, Francesca and Mooser, Catherine

Subjects:

600 Technology > 610 Medicine & health

ISSN:

0036-8075

Publisher:

American Association for the Advancement of Science

Language:

English

Submitter:

Lara Schindler

Date Deposited:

27 Jan 2020 09:51

Last Modified:

09 Mar 2020 06:59

Publisher DOI:

10.1126/science.aav3487

PubMed ID:

31727837

BORIS DOI:

10.7892/boris.138190

URI:

https://boris.unibe.ch/id/eprint/138190

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