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Signaling through IL-17C/IL-17RE Is Dispensable for Immunity to Systemic, Oral and Cutaneous Candidiasis

Conti, HR and Whibley, N and Coleman, BM and Garg, AV and Jaycox, JR and Gaffen, SL (2015) Signaling through IL-17C/IL-17RE Is Dispensable for Immunity to Systemic, Oral and Cutaneous Candidiasis. PLoS ONE, 10 (4).

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Candida albicans is a commensal fungal microbe of the human orogastrointestinal tract and skin. C . albicans causes multiple forms of disease in immunocompromised patients, including oral, vaginal, dermal and disseminated candidiasis. The cytokine IL-17 (IL-17A) and its receptor subunits, IL-17RA and IL-17RC, are required for protection to most forms of candidiasis. The importance of the IL-17R pathway has been observed not only in knockout mouse models, but also in humans with rare genetic mutations that impact generation of Th17 cells or the IL-17 signaling pathway, including Hyper-IgE Syndrome (STAT3 or TYK2 mutations) or IL17RA or ACT1 gene deficiency. The IL-17 family of cytokines is a distinct subclass of cytokines with unique structural and signaling properties. IL-17A is the bestcharacterized member of the IL-17 family to date, but far less is known about other IL-17-related cytokines. In this study, we sought to determine the role of a related IL-17 cytokine, IL-17C, in protection against oral, dermal and disseminated forms of C . albicans infection. IL-17C signals through a heterodimeric receptor composed of the IL-17RA and IL-17RE subunits. We observed that IL-17C mRNA was induced following oral C. albicans infection. However, mice lacking IL-17C or IL-17RE cleared C. albicans infections in the oral mucosa, skin and bloodstream at rates similar to WT littermate controls. Moreover, these mice demonstrated similar gene transcription profiles and recovery kinetics as WT animals. These findings indicate that IL-17C and IL-17RE are dispensable for immunity to the forms of candidiasis evaluated, and illustrate a surprisingly limited specificity of the IL-17 family of cytokines with respect to systemic, oral and cutaneous Candida infections.


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Item Type: Article
Status: Published
CreatorsEmailPitt UsernameORCID
Conti, HR
Whibley, N
Coleman, BMBIC11@pitt.eduBIC11
Garg, AV
Jaycox, JR
Gaffen, SLsarah.gaffen@pitt.eduSIG65
ContributionContributors NameEmailPitt UsernameORCID
Date: 7 April 2015
Date Type: Publication
Access Restriction: No restriction; Release the ETD for access worldwide immediately.
Journal or Publication Title: PLoS ONE
Volume: 10
Number: 4
DOI or Unique Handle: 10.1371/journal.pone.0122807
Institution: University of Pittsburgh
Schools and Programs: School of Medicine > Immunology
Refereed: Yes
Date Deposited: 23 Aug 2016 14:02
Last Modified: 30 Mar 2021 15:55


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