Requirement of interleukin-17A for systemic anti-Candida albicans host defense in mice

J Infect Dis. 2004 Aug 1;190(3):624-31. doi: 10.1086/422329. Epub 2004 Jun 22.


T cells are required for normal host defense against fungal infection, and individuals with T cell-deficiency syndromes are highly susceptible to fungal pathogens. Interleukin (IL)-17A is a proinflammatory cytokine that interconnects myeloid and lymphoid host defense. The role of murine (m) IL-17A/mIL-17A receptor (R) interactions was evaluated in a murine model of systemic candidiasis. In response to systemic challenge with Candida albicans, expression of mIL-17A was induced, and IL-17AR knockout (IL-17AR(-/-)) mice had dose-dependent, substantially reduced survival. Fungal burden in the kidneys of IL-17AR(-/-) mice was dramatically increased (25-fold at 96 h). In IL-17AR(-/-) mice, both mobilization of peripheral neutrophils and their influx to infected organs were significantly impaired and delayed. In vivo expression of mIL-17A protected normal mice from a lethal dose of C. albicans (100% at day 7 and 65% at day 42). The data suggest that the mIL-17A/mIL-17AR system is required for normal fungal host defense in vivo. IL-17A could have potential as a therapeutic cytokine for systemic C. albicans infections in immunocompromised patients with cancer or advanced acquired immunodeficiency syndrome.

Publication types

  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Animals
  • Candida albicans / pathogenicity*
  • Candidiasis / immunology*
  • Candidiasis / mortality
  • Disease Models, Animal
  • Humans
  • Interleukin-17 / metabolism*
  • Kidney / immunology
  • Kidney / microbiology
  • Mice
  • Mice, Inbred C57BL
  • Mice, Knockout
  • Receptors, Interleukin / genetics
  • Receptors, Interleukin / metabolism*
  • Receptors, Interleukin-17
  • Recombinant Proteins / genetics
  • Recombinant Proteins / metabolism*


  • IL17RA protein, human
  • Il17ra protein, mouse
  • Interleukin-17
  • Receptors, Interleukin
  • Receptors, Interleukin-17
  • Recombinant Proteins