The cytokine IL-22 promotes pathogen colonization by suppressing related commensal bacteria

Immunity. 2014 Feb 20;40(2):262-73. doi: 10.1016/j.immuni.2014.01.003. Epub 2014 Feb 6.


Interleukin-22 (IL-22) is highly induced in response to infections with a variety of pathogens, and its main functions are considered to be tissue repair and host defense at mucosal surfaces. Here we showed that IL-22 has a unique role during infection in that its expression suppressed the intestinal microbiota and enhanced the colonization of a pathogen. IL-22 induced the expression of antimicrobial proteins, including lipocalin-2 and calprotectin, which sequester essential metal ions from microbes. Because Salmonella enterica ser. Typhimurium can overcome metal ion starvation mediated by lipocalin-2 and calprotectin via alternative pathways, IL-22 boosted its colonization of the inflamed intestine by suppressing commensal Enterobacteriaceae, which are susceptible to the antimicrobial proteins. Thus, IL-22 tipped the balance between pathogenic and commensal bacteria in favor of a pathogen. Taken together, IL-22 induction can be exploited by pathogens to suppress the growth of their closest competitors, thereby enhancing pathogen colonization of mucosal surfaces.

Publication types

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

MeSH terms

  • Animals
  • Cytokines / metabolism
  • Host-Pathogen Interactions*
  • Interleukins / genetics
  • Interleukins / immunology*
  • Intestines / microbiology*
  • Mice
  • Mice, Inbred C57BL
  • Models, Biological
  • Real-Time Polymerase Chain Reaction
  • Salmonella Infections / immunology*
  • Salmonella Infections / microbiology*
  • Symbiosis / immunology*
  • Up-Regulation


  • Cytokines
  • Interleukins
  • interleukin-22