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

• Published in: PLoS pathogens Vol. 20; no. 7; p. e1012302
• Main Authors: Aggor, Felix E Y, Bertolini, Martinna, Coleman, Bianca M, Taylor, Tiffany C, Ponde, Nicole O, Gaffen, Sarah L
• Format: Journal Article
• Language: English
• Published: United States Public Library of Science 01.07.2024; Public Library of Science (PLoS)
• Subjects: Animals; Biology and Life Sciences; Candida albicans - immunology; Candidiasis; Candidiasis, Oral - immunology; Candidiasis, Oral - microbiology; Colitis; Colon; Combinatorial analysis; Cytokines; Engineering and Technology; Esophagus; Fungi; Gene expression; Health aspects; Immune response; Immunity; Interleukin 17; Interleukin 22; Interleukin-17 - immunology; Interleukin-17 - metabolism; Interleukins; Interleukins - immunology; Interleukins - metabolism; Keratin; Kinases; Lymphocytes; Lymphocytes T; Medical research; Medicine and Health Sciences; Medicine, Experimental; Mice; Mice, Inbred C57BL; Mice, Knockout; Physiological aspects; Proteins; Receptors, Interleukin - immunology; Receptors, Interleukin - metabolism; Receptors, Interleukin-17 - immunology; Receptors, Interleukin-17 - metabolism; Short Reports; Thrush (Mouth disease); Weight loss; United States
• ISSN: 1553-7374; 1553-7366; 1553-7374
• DOI: 10.1371/journal.ppat.1012302

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.