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Oral epithelial IL-22/STAT3 signaling licenses IL-17-mediated immunity to oral mucosal candidiasis

  1. Author:
    Aggor, Felix E Y [ORCID]
    Break, Timothy J
    Trevejo-Nuñez, Giraldina [ORCID]
    Whibley, Natasha [ORCID]
    Coleman, Bianca M [ORCID]
    Bailey, Rachel D [ORCID]
    Kaplan, Daniel H [ORCID]
    Naglik, Julian R [ORCID]
    Shan, Wei [ORCID]
    Shetty, Amol C [ORCID]
    McCracken, Carrie [ORCID]
    Durum,Scott
    Biswas, Partha S [ORCID]
    Bruno, Vincent M [ORCID]
    Kolls, Jay K [ORCID]
    Lionakis, Michail S
    Gaffen, Sarah L [ORCID]

  2. Author Address

    Division of Rheumatology and Clinical Immunology, University of Pittsburgh, Pittsburgh, PA, USA., Fungal Pathogenesis Section, Laboratory of Clinical Immunology and Microbiology, National Institute of Allergy and Infectious Diseases, NIH, Bethesda, MD, USA., Division of Infectious Diseases, University of Pittsburgh, Pittsburgh, PA, USA., Department of Dermatology, University of Pittsburgh, Pittsburgh, PA, USA., Department of Immunology, University of Pittsburgh, Pittsburgh, PA, USA., Centre for Host-Microbiome Interactions, Faculty of Dentistry, Oral and Craniofacial Sciences, King 39;s College London, London, UK., Cytokines and Immunity Section, Cancer and Inflammation Program, National Cancer Institute, NIH, Frederick, MD, USA., Institute for Genome Sciences, University of Maryland School of Medicine, Baltimore, MD, USA., Center for Translational Research in Infection and Inflammation, Tulane University, New Orleans, LA, USA., Division of Rheumatology and Clinical Immunology, University of Pittsburgh, Pittsburgh, PA, USA. sarah.gaffen@pitt.edu.,
    1. Year: 2020
    2. Date: Jun 05
  2. Journal: Science immunology
    1. 5
    2. 48
    3. Pages: pii: eaba0570
  4. Type of Article: Article
  5. Article Number: eaba0570
  6. ISSN: 2470-9468
  1. Abstract:

    Oropharyngeal candidiasis (OPC; thrush) is an opportunistic infection caused by the commensal fungus Candida albicans Interleukin-17 (IL-17) and IL-22 are cytokines produced by type 17 lymphocytes. Both cytokines mediate antifungal immunity yet activate quite distinct downstream signaling pathways. While much is now understood about how IL-17 promotes immunity in OPC, the activities of IL-22 are far less well delineated. We show that, despite having similar requirements for induction from type 17 cells, IL-22 and IL-17 function nonredundantly during OPC. We find that the IL-22 and IL-17 receptors are required in anatomically distinct locations within the oral mucosa; loss of IL-22RA1 or signal transducer and activator of transcription 3 (STAT3) in the oral basal epithelial layer (BEL) causes susceptibility to OPC, whereas IL-17RA is needed in the suprabasal epithelial layer (SEL). Transcriptional profiling of the tongue linked IL-22/STAT3 not only to oral epithelial cell proliferation and survival but also, unexpectedly, to driving an IL-17-specific gene signature. We show that IL-22 mediates regenerative signals on the BEL that replenish the IL-17RA-expressing SEL, thereby restoring the ability of the oral epithelium to respond to IL-17 and thus to mediate antifungal events. Consequently, IL-22 signaling in BEL "licenses" IL-17 signaling in the oral mucosa, revealing spatially distinct yet cooperative activities of IL-22 and IL-17 in oral candidiasis. Copyright © 2020 The Authors, some rights reserved; exclusive licensee American Association for the Advancement of Science. No claim to original U.S. Government Works.

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External Sources

  1. View Full Text
  2. DOI: 10.1126/sciimmunol.aba0570
  3. PMID: 32503875
  4. View record in Web of Science®
  5. WOS: 000546993600003
  6. PII : 5/48/eaba0570

Library Notes

  1. Fiscal Year: FY2019-2020
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