Autoimmune host-microbiota interactions at barrier sites and beyond

Trends Mol Med. 2015 Apr;21(4):233-44. doi: 10.1016/j.molmed.2015.02.006. Epub 2015 Mar 11.


The microbiota is considered to be an important factor influencing the pathogenesis of autoimmunity at both barrier sites and internal organs. Impinging on innate and adaptive immunity, commensals exert protective or detrimental effects on various autoimmune animal models. Human microbiome studies of autoimmunity remain largely descriptive, but suggest a role for dysbiosis in autoimmune disease. Humanized gnotobiotic approaches have advanced our understanding of immune-commensal interactions, but little is known about the mechanisms in autoimmunity. We propose that, similarly to infectious agents, the microbiota mediates autoimmunity via bystander activation, epitope spread, and, particularly under homeostatic conditions, via crossreactivity. This review presents an overview of the current literature concluding with outstanding questions in this field.

Keywords: bystander activation; commensal; crossreactivity; epitope spread; microbiome; molecular mimicry.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't
  • Review

MeSH terms

  • Adaptive Immunity
  • Animals
  • Autoimmune Diseases / immunology
  • Autoimmune Diseases / microbiology*
  • Autoimmunity*
  • Disease Models, Animal
  • Homeostasis
  • Host-Pathogen Interactions / immunology*
  • Humans
  • Inflammatory Bowel Diseases / genetics
  • Inflammatory Bowel Diseases / immunology
  • Intestines / microbiology
  • Microbiota*