Interleukin-22 induces interleukin-18 expression from epithelial cells during intestinal infection

Immunity. 2015 Feb 17;42(2):321-331. doi: 10.1016/j.immuni.2015.01.011. Epub 2015 Feb 10.

Abstract

T helper 1 (Th1) cell-associated immunity exacerbates ileitis induced by oral Toxoplasma gondii infection. We show here that attenuated ileitis observed in interleukin-22 (IL-22)-deficient mice was associated with reduced production of Th1-cell-promoting IL-18. IL-22 not only augmented the expression of Il18 mRNA and inactive precursor protein (proIL-18) in intestinal epithelial cells after T. gondii or Citrobacter rodentium infection, but also maintained the homeostatic amount of proIL-18 in the ileum. IL-22, however, did not induce the processing to active IL-18, suggesting a two-step regulation of IL-18 in these cells. Although IL-18 exerted pathogenic functions during ileitis triggered by T. gondii, it was required for host defense against C. rodentium. Conversely, IL-18 was required for the expression of IL-22 in innate lymphoid cells (ILCs) upon T. gondii infection. Our results define IL-18 as an IL-22 target gene in epithelial cells and describe a complex mutual regulation of both cytokines during intestinal infection.

MeSH terms

  • Animals
  • Cells, Cultured
  • Citrobacter rodentium / immunology
  • Enterobacteriaceae Infections / immunology*
  • Enterobacteriaceae Infections / microbiology
  • Epithelial Cells / immunology
  • Ileitis / immunology
  • Ileitis / microbiology
  • Ileitis / parasitology
  • Ileum / immunology
  • Ileum / microbiology
  • Ileum / parasitology
  • Inflammation / immunology
  • Interferon-gamma / biosynthesis
  • Interleukin-18 / biosynthesis
  • Interleukin-18 / immunology*
  • Interleukins / genetics
  • Interleukins / immunology*
  • Intestinal Mucosa / immunology*
  • Intestinal Mucosa / microbiology
  • Intestinal Mucosa / parasitology
  • Mice
  • Mice, Inbred C57BL
  • Mice, Knockout
  • Neutrophil Infiltration / immunology
  • Neutrophils / immunology
  • Organ Culture Techniques
  • RNA, Messenger / biosynthesis
  • Th1 Cells / immunology
  • Toxoplasma / immunology
  • Toxoplasmosis / immunology*
  • Toxoplasmosis / parasitology
  • Up-Regulation

Substances

  • Interleukin-18
  • Interleukins
  • RNA, Messenger
  • Interferon-gamma
  • interleukin-22

Associated data

  • GEO/GSE65472