IL-17 regulates systemic fungal immunity by controlling the functional competence of NK cells

Immunity. 2014 Jan 16;40(1):117-27. doi: 10.1016/j.immuni.2013.12.002. Epub 2014 Jan 9.


Interleukin 17 (IL-17)-mediated immunity plays a key role in protection from fungal infections in mice and man. Here, we confirmed that mice deficient in the IL-17 receptor or lacking the ability to secrete IL-17 are highly susceptible to systemic candidiasis, but we found that temporary blockade of the IL-17 pathway during infection in wild-type mice did not impact fungal control. Rather, mice lacking IL-17 receptor signaling had a cell-intrinsic impairment in the development of functional NK cells, which accounted for the susceptibility of these mice to systemic fungal infection. NK cells promoted antifungal immunity by secreting GM-CSF, necessary for the fungicidal activity of neutrophils. These data reveal that NK cells are crucial for antifungal defense and indicate a role for IL-17 family cytokines in NK cell development. The IL-17-NK cell axis may impact immunity against not only fungi but also bacteria, viruses, and tumors.

Publication types

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

MeSH terms

  • Animals
  • Candidiasis / genetics
  • Candidiasis / immunology*
  • Cell Differentiation
  • Cells, Cultured
  • Cytotoxicity, Immunologic
  • Disease Susceptibility
  • Granulocyte-Macrophage Colony-Stimulating Factor / metabolism*
  • Interleukin-17 / genetics
  • Interleukin-17 / metabolism
  • Killer Cells, Natural / immunology*
  • Mice
  • Mice, Inbred C57BL
  • Mice, Knockout
  • Neutrophils / immunology*
  • Receptors, Interleukin-17 / genetics
  • Receptors, Interleukin-17 / metabolism*
  • Signal Transduction / genetics


  • Interleukin-17
  • Receptors, Interleukin-17
  • Granulocyte-Macrophage Colony-Stimulating Factor