Innate lymphoid cells promote anatomical containment of lymphoid-resident commensal bacteria

Science. 2012 Jun 8;336(6086):1321-5. doi: 10.1126/science.1222551. Epub 2012 Jun 6.

Abstract

The mammalian intestinal tract is colonized by trillions of beneficial commensal bacteria that are anatomically restricted to specific niches. However, the mechanisms that regulate anatomical containment remain unclear. Here, we show that interleukin-22 (IL-22)-producing innate lymphoid cells (ILCs) are present in intestinal tissues of healthy mammals. Depletion of ILCs resulted in peripheral dissemination of commensal bacteria and systemic inflammation, which was prevented by administration of IL-22. Disseminating bacteria were identified as Alcaligenes species originating from host lymphoid tissues. Alcaligenes was sufficient to promote systemic inflammation after ILC depletion in mice, and Alcaligenes-specific systemic immune responses were associated with Crohn's disease and progressive hepatitis C virus infection in patients. Collectively, these data indicate that ILCs regulate selective containment of lymphoid-resident bacteria to prevent systemic inflammation associated with chronic diseases.

Publication types

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

MeSH terms

  • Adult
  • Alcaligenes / immunology
  • Alcaligenes / isolation & purification
  • Alcaligenes / physiology*
  • Animals
  • Bacterial Translocation
  • Crohn Disease / immunology
  • Crohn Disease / microbiology
  • Hepatitis C, Chronic / immunology
  • Hepatitis C, Chronic / microbiology
  • Humans
  • Immunity, Innate
  • Inflammation
  • Interleukins / administration & dosage
  • Interleukins / biosynthesis
  • Interleukins / immunology*
  • Intestines / immunology*
  • Intestines / microbiology
  • Leukocyte L1 Antigen Complex / metabolism
  • Liver / microbiology
  • Lymph Nodes / immunology
  • Lymphocytes / immunology*
  • Lymphoid Tissue / immunology*
  • Lymphoid Tissue / microbiology*
  • Macaca mulatta
  • Mice
  • Mice, Inbred C57BL
  • Middle Aged
  • Spleen / microbiology
  • Young Adult

Substances

  • Interleukins
  • Leukocyte L1 Antigen Complex
  • interleukin-22