Microbiota-derived peptide mimics drive lethal inflammatory cardiomyopathy

Area of Science:

• Immunology
• Microbiology
• Cardiology

Background:

• Myocarditis can progress to inflammatory cardiomyopathy via T helper 1 and T helper 17 cell stimulation.
• The mechanisms behind heart-specific T cell cardiotoxicity programming remain unclear.

Purpose of the Study:

• To elucidate the mechanisms of cardiotoxicity in autoimmune myocarditis.
• To investigate the role of gut microbiota in the development of inflammatory cardiomyopathy.

Main Methods:

• Utilized a mouse model of spontaneous autoimmune myocarditis.
• Analyzed T helper cell responses and bacterial mimic peptides.
• Examined human patient data for T cell and B cell responses.

Main Results:

• Progression to lethal heart disease was dependent on cardiac myosin-specific T helper 17 cells.
• These T helper 17 cells were imprinted in the intestine by a commensal Bacteroides species peptide mimic.
• Antibiotic therapy prevented lethal disease in mice.
• Human myocarditis patients showed elevated Bacteroides-specific CD4+ T cell and B cell responses.

Conclusions:

• Commensal bacteria-derived mimic peptides can promote inflammatory cardiomyopathy in susceptible individuals.
• The microbiome can be manipulated to restrain cardiotoxic T cells.
• Inflammatory cardiomyopathy is a targetable disease through microbiome modulation.