IL-23 and the Th17 pathway promote inflammation and impair antifungal immune resistance

Eur J Immunol. 2007 Oct;37(10):2695-706. doi: 10.1002/eji.200737409.


Although inflammation is an essential component of the protective response to fungi, its dysregulation may significantly worsen fungal diseases. We found here that the IL-23/IL-17 developmental pathway acted as a negative regulator of the Th1-mediated immune resistance to fungi and played an inflammatory role previously attributed to uncontrolled Th1 cell responses. Both inflammation and infection were exacerbated by a heightened Th17 response against Candida albicans and Aspergillus fumigatus, two major human fungal pathogens. IL-23 acted as a molecular connection between uncontrolled fungal growth and inflammation, being produced by dendritic cells in response to a high fungal burden and counter-regulating IL-12p70 production. Both IL-23 and IL-17 subverted the inflammatory program of neutrophils, which resulted in severe tissue inflammatory pathology associated with infection. Our data are the first demonstrating that the IL-23/IL-17 pathway promotes inflammation and susceptibility in an infectious disease model. As IL-23-driven inflammation promotes infection and impairs antifungal resistance, modulation of the inflammatory response represents a potential strategy to stimulate protective immune responses to fungi.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Aspergillosis / immunology*
  • Aspergillosis / pathology
  • Aspergillus fumigatus / immunology
  • Candida albicans / immunology
  • Candidiasis / immunology*
  • Candidiasis / pathology
  • Cells, Cultured
  • Female
  • Immunity, Innate*
  • Inflammation / immunology
  • Interleukin-17 / physiology*
  • Interleukin-23 / physiology*
  • Mice
  • Mice, Inbred BALB C
  • Mice, Inbred C57BL
  • Mice, Knockout
  • Signal Transduction / immunology*


  • Interleukin-17
  • Interleukin-23