MyD88 signaling in T cells directs IgA-mediated control of the microbiota to promote health

Cell Host Microbe. 2015 Feb 11;17(2):153-63. doi: 10.1016/j.chom.2014.12.009. Epub 2015 Jan 22.

Abstract

Altered commensal communities are associated with human disease. IgA mediates intestinal homeostasis and regulates microbiota composition. Intestinal IgA is produced at high levels as a result of T follicular helper cell (TFH) and B cell interactions in germinal centers. However, the pathways directing host IgA responses toward the microbiota remain unknown. Here, we report that signaling through the innate adaptor MyD88 in gut T cells coordinates germinal center responses, including TFH and IgA+ B cell development. TFH development is deficient in germ-free mice and can be restored by feeding TLR2 agonists that activate T cell-intrinsic MyD88 signaling. Loss of this pathway diminishes high-affinity IgA targeting of the microbiota and fails to control the bacterial community, leading to worsened disease. Our findings identify that T cells converge innate and adaptive immune signals to coordinate IgA against the microbiota, constraining microbial community membership to promote symbiosis.

Publication types

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

MeSH terms

  • Adaptive Immunity
  • Animals
  • B-Lymphocytes / immunology
  • Gastrointestinal Microbiome / immunology*
  • Homeostasis
  • Immunity, Innate
  • Immunoglobulin A / immunology*
  • Intestinal Mucosa / immunology*
  • Intestinal Mucosa / microbiology
  • Mice
  • Myeloid Differentiation Factor 88 / metabolism*
  • Signal Transduction*
  • T-Lymphocytes / immunology*

Substances

  • Immunoglobulin A
  • MYD88 protein, human
  • Myeloid Differentiation Factor 88

Associated data

  • SRA/SRP050978