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- Title
Combinatorial actions of IL-22 and IL-17 drive optimal immunity to oral candidiasis through SPRRs.
- Authors
Aggor, Felix E. Y.; Bertolini, Martinna; Coleman, Bianca M.; Taylor, Tiffany C.; Ponde, Nicole O.; Gaffen, Sarah L.
- Abstract
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. Author summary: Oral thrush is a painful oral infection of the mouth. We show that the combined actions of 2 immune cytokines, IL-17 and IL-22, act in a concerted manner to combat this infection, in part via small proline rich proteins.
- Subjects
THRUSH (Mouth disease); INTERLEUKIN-17; IMMUNITY; WEIGHT loss; T cells; INFLAMMATORY bowel diseases; MYCOSES
- Publication
PLoS Pathogens, 2024, Vol 0, Issue 7, p1
- ISSN
1553-7366
- Publication type
Article
- DOI
10.1371/journal.ppat.1012302