Combinatorial actions of IL-22 and IL-17 drive optimal immunity to oral candidiasis through SPRRs.

Oropharyngeal candidiasis (OPC) is the most common human fungal infection, arising typically from T cell immune impairments. IL-17 and IL-22 contribute individually to OPC responses, but here we demonstrate that the combined actions of both cytokines are essential for resistance to OPC. Mice lacking...

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Bibliographic Details
Main Authors: Felix E Y Aggor, Martinna Bertolini, Bianca M Coleman, Tiffany C Taylor, Nicole O Ponde, Sarah L Gaffen
Format: Article
Language:English
Published: Public Library of Science (PLoS) 2024-07-01
Series:PLoS Pathogens
Online Access:https://journals.plos.org/plospathogens/article/file?id=10.1371/journal.ppat.1012302&type=printable
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Summary:Oropharyngeal candidiasis (OPC) is the most common human fungal infection, arising typically from T cell immune impairments. IL-17 and IL-22 contribute individually to OPC responses, but here we demonstrate that the combined actions of both cytokines are essential for resistance to OPC. Mice lacking IL-17RA and IL-22RA1 exhibited high fungal loads in esophagus- and intestinal tract, severe weight loss, and symptoms of colitis. Ultimately, mice succumbed to infection. Dual loss of IL-17RA and IL-22RA impaired expression of small proline rich proteins (SPRRs), a class of antimicrobial effectors not previously linked to fungal immunity. Sprr2a1 exhibited direct candidacidal activity in vitro, and Sprr1-3a-/- mice were susceptible to OPC. Thus, cooperative actions of Type 17 cytokines mediate oral mucosal anti-Candida defenses and reveal a role for SPRRs.
ISSN:1553-7366
1553-7374