Regulation of autoimmune myocarditis by host responses to the microbiome

Jobert G. Barin, Monica V. Talor, Nicola L. Diny, Su Fey Ong, Julie A. Schaub, Elizabeth Gebremariam, Djahida Bedja, Guobao Chen, Hee Sun Choi, Xuezhou Hou, Lei Wu, Ashley B. Cardamone, Daniel A. Peterson, Noel R. Rose, Daniela Čiháková*

*Corresponding author for this work

Research output: Contribution to journalArticle

1 Citation (Scopus)

Abstract

The extensive, diverse communities that constitute the microbiome are increasingly appreciated as important regulators of human health and disease through inflammatory, immune, and metabolic pathways. We sought to elucidate pathways by which microbiota contribute to inflammatory, autoimmune cardiac disease. We employed an animal model of experimental autoimmune myocarditis (EAM), which results in inflammatory and autoimmune pathophysiology and subsequent maladaptive cardiac remodeling and heart failure. Antibiotic dysbiosis protected mice from EAM and fibrotic cardiac dysfunction. Additionally, mice derived from different sources with different microbiome colonization profiles demonstrated variable susceptibility to disease. Unexpectedly, it did not track with segmented filamentous bacteria (SFB)-driven Th17 programming of CD4+ T cells in the steady-state gut. Instead, we found disease susceptibility to track with presence of type 3 innate lymphoid cells (ILC3s). Ablating ILCs by antibody depletion or genetic tools in adoptive transfer variants of the EAM model demonstrated that ILCs and microbiome profiles contributed to the induction of CCL20/CCR6-mediated inflammatory chemotaxis to the diseased heart. From these data, we conclude that sensing of the microbiome by ILCs is an important checkpoint in the development of inflammatory cardiac disease processes through their ability to elicit cardiotropic chemotaxis.

Original languageEnglish
Pages (from-to)141-152
Number of pages12
JournalExperimental and Molecular Pathology
Volume103
Issue number2
DOIs
Publication statusPublished - 1 Oct 2017
Externally publishedYes

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Keywords

  • autoimmune disease
  • chemokines
  • innate lymphoid cells
  • microbiome
  • myocarditis
  • segmented filamentous bacteria
  • Th17 cells

Cite this

Barin, J. G., Talor, M. V., Diny, N. L., Ong, S. F., Schaub, J. A., Gebremariam, E., ... Čiháková, D. (2017). Regulation of autoimmune myocarditis by host responses to the microbiome. Experimental and Molecular Pathology, 103(2), 141-152. https://doi.org/10.1016/j.yexmp.2017.08.003