title: IL-17 regulates systemic fungal immunity by controlling the functional competence of NK cells.
abstract: 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.
authors.affiliation: Institute of Microbiology, ETH Zurich, Vladimir-Prelog-Weg 4, 8093 Zürich, Switzerland.
authors.forename: Eva
authors.initials: E
authors.lastname: Bär
authors.affiliation: Immunobiology Laboratory, Cancer Research UK, London Research Institute, Lincoln's Inn Fields Laboratories, 44 Lincoln's Inn Fields, London WC2A 3LY, UK.
authors.forename: Paul G
authors.initials: PG
authors.lastname: Whitney
authors.affiliation: Institute of Microbiology, ETH Zurich, Vladimir-Prelog-Weg 4, 8093 Zürich, Switzerland.
authors.forename: Kathrin
authors.initials: K
authors.lastname: Moor
authors.affiliation: Immunobiology Laboratory, Cancer Research UK, London Research Institute, Lincoln's Inn Fields Laboratories, 44 Lincoln's Inn Fields, London WC2A 3LY, UK.
authors.forename: Caetano
authors.initials: C
authors.lastname: Reis e Sousa
authors.affiliation: Institute of Microbiology, ETH Zurich, Vladimir-Prelog-Weg 4, 8093 Zürich, Switzerland. Electronic address: leibundgut@micro.biol.ethz.ch.
authors.forename: Salomé
authors.initials: S
authors.lastname: LeibundGut-Landmann
mesh_terms: D000818:Animals; D002177:Candidiasis / Q000235:genetics / Q000276:immunology*; D002454:Cell Differentiation; D002478:Cells, Cultured; D003602:Cytotoxicity, Immunologic; D004198:Disease Susceptibility; D016178:Granulocyte-Macrophage Colony-Stimulating Factor / Q000378:metabolism*; D020381:Interleukin-17 / Q000235:genetics / Q000378:metabolism; D007694:Killer Cells, Natural / Q000276:immunology*; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D009504:Neutrophils / Q000276:immunology*; D053722:Receptors, Interleukin-17 / Q000235:genetics / Q000378:metabolism*; D015398:Signal Transduction / Q000235:genetics
chemical_list: D020381:Interleukin-17; D053722:Receptors, Interleukin-17; D016178:Granulocyte-Macrophage Colony-Stimulating Factor