Microbial colonization drives expansion of IL-1 receptor 1-expressing and IL-17-producing gamma/delta T cells

Cell Host Microbe. 2010 Feb 18;7(2):140-50. doi: 10.1016/j.chom.2010.01.005.

Abstract

IL-17 cytokine production by the Th17 T cell subset is regulated by intestinal commmensals. We show that microbial colonization also regulates innate IL-17 production. A population of CD62L(-) gamma/delta T cells, in particular a lineage expressing the IL-1 receptor 1 (IL-1R1), can be quickly activated by microbes to produce IL-17. Antibiotic treatment and monocolonization of mice suggest that specific commensals-but not metronidazole-sensitive anaerobes like Bacteroides species-are required for maintaining IL-1R1(+) gamma/delta T cells. Signaling through the guanine nucleotide exchange factor VAV1, but not through Toll-like receptors or antigen presentation pathways, is essential for inducing IL-1R1(+) gamma/delta T cells. Furthermore, IL-1R1(+) gamma/delta T cells are a potential source of IL-17 that can be activated by IL-23 and IL-1 in both infectious and noninfectious settings in vitro and in vivo. Thus, commensals orchestrate the expansion of phenotypically distinct gammadelta T cells, and innate immunity is a three-way interaction between host, pathogens, and microbiota.

Publication types

  • Research Support, N.I.H., Extramural

MeSH terms

  • Animals
  • Bacteria / immunology*
  • Cell Proliferation
  • Gastrointestinal Tract / microbiology*
  • Interleukin-17 / biosynthesis*
  • Male
  • Mice
  • Mice, Inbred C57BL
  • Mice, Knockout
  • Models, Biological
  • Receptors, Antigen, T-Cell, gamma-delta / analysis*
  • Receptors, Interleukin-1 / analysis*
  • T-Lymphocyte Subsets / chemistry
  • T-Lymphocyte Subsets / immunology*
  • T-Lymphocytes / chemistry
  • T-Lymphocytes / immunology*

Substances

  • Interleukin-17
  • Receptors, Antigen, T-Cell, gamma-delta
  • Receptors, Interleukin-1