title: IL-17-mediated antifungal defense in the oral mucosa is independent of neutrophils.
abstract: Interleukin-17 (IL-17)-mediated immunity has emerged as a crucial host defense mechanism against Candida albicans infections in mucosal tissues and the skin. The precise mechanism by which the IL-17 pathway prevents fungal outgrowth has not been clarified. Neutrophils are critical for limiting fungal dissemination and IL-17 is generally thought to act by regulating neutrophil mobilization and trafficking to the site of infection. Using a mouse model of oropharyngeal candidiasis (OPC), we found that strikingly the IL-17 pathway is not required for the neutrophil response to C. albicans. Mice deficient for the IL-17 receptor subunits IL-17 receptor A (IL-17RA) or IL-17RC or mice depleted of IL-17A and IL-17F exhibited a normal granulocyte colony-stimulating factor (G-CSF) and CXC-chemokine response and displayed no defect in neutrophil recruitment or function. Instead, the inability of these mice to clear the fungus was associated with a selective defect in the induction of antimicrobial peptides (AMPs) in the epithelium that resulted in persistent fungal colonization. Importantly, this antifungal mechanism of IL-17A and IL-17F did not extend to the closely related family member IL-17C. Together, these data uncouple IL-17-dependent effector mechanisms from the neutrophil response and reveal a compartmentalization of the antifungal defense in the oral mucosa providing a new understanding of IL-17-mediated mucosal immunity against C. albicans.
authors.affiliation: Institute of Microbiology, ETH Zürich, Zürich, Switzerland.
authors.forename: K
authors.initials: K
authors.lastname: Trautwein-Weidner
authors.affiliation: Institute of Microbiology, ETH Zürich, Zürich, Switzerland.
authors.forename: A
authors.initials: A
authors.lastname: Gladiator
authors.affiliation: Institute of Microbiology, ETH Zürich, Zürich, Switzerland.
authors.forename: S
authors.initials: S
authors.lastname: Nur
authors.affiliation: Institute of Microbiology, ETH Zürich, Zürich, Switzerland.
authors.forename: P
authors.initials: P
authors.lastname: Diethelm
authors.affiliation: Institute of Microbiology, ETH Zürich, Zürich, Switzerland.
authors.forename: S
authors.initials: S
authors.lastname: LeibundGut-Landmann
mesh_terms: D000818:Animals; D002176:Candida albicans / Q000276:immunology; D002180:Candidiasis, Oral / Q000276:immunology / Q000378:metabolism / Q000382:microbiology; D004195:Disease Models, Animal; D005658:Fungi / Q000276:immunology*; D016130:Immunophenotyping; D020381:Interleukin-17 / Q000172:deficiency / Q000235:genetics / Q000378:metabolism*; D051379:Mice; D018345:Mice, Knockout; D009061:Mouth Mucosa / Q000276:immunology* / Q000378:metabolism* / Q000382:microbiology / Q000473:pathology; D009181:Mycoses / Q000276:immunology / Q000378:metabolism / Q000382:microbiology; D009504:Neutrophils / Q000276:immunology* / Q000378:metabolism* / Q000382:microbiology; D010641:Phenotype; D015398:Signal Transduction
chemical_list: D020381:Interleukin-17