IL-22 defines a novel immune pathway of antifungal resistance

Mucosal Immunol. 2010 Jul;3(4):361-73. doi: 10.1038/mi.2010.22. Epub 2010 May 5.

Abstract

The role of IL-17 and Th17 cells in immunity vs. pathology associated with the human commensal Candida albicans remains controversial. Both positive and negative effects on immune resistance have been attributed to IL-17/Th17 in experimental candidiasis. In this study, we provide evidence that IL-22, which is also produced by Th17 cells, has a critical, first-line defense in candidiasis by controlling the growth of infecting yeasts as well as by contributing to the host's epithelial integrity in the absence of acquired Th1-type immunity. The two pathways are reciprocally regulated, and IL-22 is upregulated under Th1 deficiency conditions and vice versa. Whereas both IL-17A and F are dispensable for antifungal resistance, IL-22 mediates protection in IL-17RA-deficient mice, in which IL-17A contributes to disease susceptibility. Thus, our findings suggest that protective immunity to candidiasis is made up of a staged response involving an early, IL-22-dominated response followed by Th1/Treg reactivity that will prevent fungal dissemination and supply memory.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Candida albicans / growth & development
  • Candida albicans / immunology*
  • Candida albicans / pathogenicity
  • Candidiasis / genetics
  • Candidiasis / immunology*
  • Candidiasis / metabolism
  • Candidiasis / pathology
  • Cell Growth Processes
  • Cells, Cultured
  • Humans
  • Immunity, Mucosal
  • Interleukin-17 / genetics
  • Interleukin-17 / immunology
  • Interleukin-17 / metabolism
  • Interleukins / genetics
  • Interleukins / immunology
  • Interleukins / metabolism*
  • Intestinal Mucosa / immunology*
  • Intestinal Mucosa / metabolism
  • Intestinal Mucosa / microbiology
  • Intestinal Mucosa / pathology
  • Mice
  • Mice, Inbred BALB C
  • Mice, Inbred C57BL
  • Mice, Knockout
  • Models, Animal
  • Receptors, Interleukin-17 / genetics
  • Receptors, Interleukin-17 / metabolism
  • Th1 Cells / immunology*
  • Th1 Cells / microbiology
  • Th2 Cells / immunology
  • Th2 Cells / microbiology

Substances

  • Il17ra protein, mouse
  • Interleukin-17
  • Interleukins
  • Receptors, Interleukin-17
  • interleukin-22