Microbiota-derived peptide mimics drive lethal inflammatory cardiomyopathy

Publication

Microbiota-derived peptide mimics drive lethal inflammatory cardiomyopathy

Journal Paper/Review - Nov 15, 2019

Gil Cruz Cristina, Jahns Roland, Wyss Madeleine, Mooser Catherine, Lambrecht Bart N, Maeder Micha, Rickli Hans, Flatz Lukas, Eriksson Urs, Geuking Markus B, McCoy Kathy D, Boivin-Jahns Valérie, Slack Emma M C, Arnoldini Markus, Pérez Shibayama Christian Ivan, De Martin Angelina, Ronchi Francesca, Van der Borght Katrien, Niederer Rebekka, Onder Lucas, Lütge Mechthild, Novkovic Mario, Nindl Veronika, Ramos Gustavo, Ludewig Burkhard

Units

Institute of Immunobiology, Medizinisches Forschungszentrum, Kardiologie, Dermatologie | Venerologie | Allergologie

Keywords

Link to Abstract: http://science.sciencemag.org/cgi/content/abstract/366/6467/881?ijkey=prWyn9fm3ctEE&keytype=ref&siteid=sci

Link to Reprint: http://science.sciencemag.org/cgi/rapidpdf/366/6467/881?ijkey=prWyn9fm3ctEE&keytype=ref&siteid=sci

Citation

Gil Cruz C, Jahns R, Wyss M, Mooser C, Lambrecht B, Maeder M, Rickli H, Flatz L, Eriksson U, Geuking M, McCoy K, Boivin-Jahns V, Slack E, Arnoldini M, Pérez Shibayama C, De Martin A, Ronchi F, Van der Borght K, Niederer R, Onder L, Lütge M, Novkovic M, Nindl V, Ramos G, Ludewig B. Microbiota-derived peptide mimics drive lethal inflammatory cardiomyopathy. Science 2019; 366:881-886.

Type

Journal Paper/Review (English)

Journal

Science 2019; 366

Publication Date

Nov 15, 2019

Issn Electronic

1095-9203

Pages

881-886

Brief description/objective

Myocarditis can develop into inflammatory cardiomyopathy through chronic stimulation of myosin heavy chain 6-specific T helper (T)1 and T17 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 T17 cells imprinted in the intestine by a commensal species peptide mimic. Both the successful prevention of lethal disease in mice by antibiotic therapy and the significantly elevated 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.