IL-17-mediated antifungal defense in the oral mucosa is independent of neutrophils

K Trautwein-Weidner, A Gladiator, S Nur… - Mucosal …, 2015 - nature.com
K Trautwein-Weidner, A Gladiator, S Nur, P Diethelm, S LeibundGut-Landmann
Mucosal immunology, 2015nature.com
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 …
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.
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