title: Vaccine-induced protection against 3 systemic mycoses endemic to North America requires Th17 cells in mice.
abstract: Worldwide rates of systemic fungal infections, including three of the major pathogens responsible for such infections in North America (Coccidioides posadasii, Histoplasma capsulatum, and Blastomyces dermatitidis), have soared recently, spurring interest in developing vaccines. The development of Th1 cells is believed to be crucial for protective immunity against pathogenic fungi, whereas the role of Th17 cells is vigorously debated. In models of primary fungal infection, some studies have shown that Th17 cells mediate resistance, while others have shown that they promote disease pathology. Here, we have shown that Th1 immunity is dispensable and that fungus-specific Th17 cells are sufficient for vaccine-induced protection against lethal pulmonary infection with B. dermatitidis in mice. Further, vaccine-induced Th17 cells were necessary and sufficient to protect against the three major systemic mycoses in North America. Mechanistically, Th17 cells engendered protection by recruiting and activating neutrophils and macrophages to the alveolar space, while the induction of Th17 cells and acquisition of vaccine immunity unexpectedly required the adapter molecule Myd88 but not the fungal pathogen recognition receptor Dectin-1. These data suggest that human vaccines against systemic fungal infections should be designed to induce Th17 cells if they are to be effective.
authors.affiliation: Department of Pediatrics, University of Wisconsin School of Medicine and Public Health, Madison, Wisconsin 53706, USA. mwuethri@wisc.edu
authors.forename: Marcel
authors.initials: M
authors.lastname: Wüthrich
authors.forename: Benjamin
authors.initials: B
authors.lastname: Gern
authors.forename: Chiung Yu
authors.initials: CY
authors.lastname: Hung
authors.forename: Karen
authors.initials: K
authors.lastname: Ersland
authors.forename: Nicole
authors.initials: N
authors.lastname: Rocco
authors.forename: John
authors.initials: J
authors.lastname: Pick-Jacobs
authors.forename: Kevin
authors.initials: K
authors.lastname: Galles
authors.forename: Hanna
authors.initials: H
authors.lastname: Filutowicz
authors.forename: Thomas
authors.initials: T
authors.lastname: Warner
authors.forename: Michael
authors.initials: M
authors.lastname: Evans
authors.forename: Garry
authors.initials: G
authors.lastname: Cole
authors.forename: Bruce
authors.initials: B
authors.lastname: Klein
mesh_terms: D000818:Animals; D005657:Fungal Vaccines / Q000276:immunology*; D006801:Humans; D020381:Interleukin-17 / Q000235:genetics / Q000276:immunology; D037181:Lectins, C-Type; D008213:Lymphocyte Activation / Q000276:immunology; D008264:Macrophages / Q000166:cytology / Q000276:immunology; D008565:Membrane Proteins / Q000276:immunology; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D009181:Mycoses / Q000276:immunology* / Q000517:prevention & control*; D009419:Nerve Tissue Proteins / Q000276:immunology; D009504:Neutrophils / Q000166:cytology / Q000276:immunology; D009656:North America; D053722:Receptors, Interleukin-17 / Q000276:immunology; D018417:Th1 Cells / Q000276:immunology; D058504:Th17 Cells / Q000276:immunology*; D000099181:Dectin-1
chemical_list: D005657:Fungal Vaccines; D020381:Interleukin-17; D037181:Lectins, C-Type; D008565:Membrane Proteins; D009419:Nerve Tissue Proteins; D053722:Receptors, Interleukin-17; D000099181:Dectin-1