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Pathogens 2015, 4(3), 559-572; doi:10.3390/pathogens4030559

Neutrophils Do Not Express IL-17A in the Context of Acute Oropharyngeal Candidiasis

1
Children's Hospital of Pittsburgh of UPMC, Department of Pediatrics, Pittsburgh, PA 15224, USA
2
Medical College of Wisconsin, Department of Pediatrics, Division of Infectious Diseases, Milwaukee, WI 53201, USA
3
Department of Medicine, Division of Rheumatology & Clinical Immunology, University of Pittsburgh, BST S702, 200 Lothrop Street, Pittsburgh, PA 15261, USA
*
Author to whom correspondence should be addressed.
Academic Editor: Lawrence S. Young
Received: 22 June 2015 / Revised: 13 July 2015 / Accepted: 21 July 2015 / Published: 24 July 2015
(This article belongs to the Special Issue Candida Albicans Infections)
View Full-Text   |   Download PDF [727 KB, uploaded 24 July 2015]   |  

Abstract

IL-17 protects against pathogens by acting on nonhematopoietic cells to induce neutrophil recruitment through upregulation of chemokines and G-CSF. IL-17- and Th17-deficient humans and mice are susceptible to mucosal Candida albicans infections, linked to impaired neutrophil responses. IL-17 production is traditionally associated with CD4+ Th17 cells. However, IL-17 is also expressed during innate responses to facilitate rapid pathogen clearance. Innate IL-17-expressing cells include various lymphocyte-type subsets, including ILC3, NKT, γδ-T and “natural” Th17 (nTh17) cells. Some reports suggest that neutrophils can express IL-17 during fungal infections. Here, we asked whether neutrophils serve as a source of IL-17 during acute oropharyngeal candidiasis (OPC) using an IL-17A fate-tracking reporter mouse. Mice were subjected to OPC for two days, and oral tissue was analyzed by flow cytometry. IL-17A was expressed by γδ-T cells and TCRβ+ natural Th17 (nTh17) cells, as recently reported. Although infiltrating neutrophils were recruited to the tongue following infection, they did not express the IL-17A reporter. Moreover, neutrophil-depleted mice exhibited normal transcription of both Il17a and downstream IL-17-dependent gene targets after Candida challenge. Thus, in acute OPC, neutrophils are not a measurable source of IL-17 production, nor are they necessary to trigger IL-17-dependent gene expression, although they are essential for ultimate pathogen control. View Full-Text
Keywords: IL-17; Th17; Candida albicans; neutrophils; fungal infection; oral candidiasis; innate lymphocyte; TCR; γδ-T cell; mice IL-17; Th17; Candida albicans; neutrophils; fungal infection; oral candidiasis; innate lymphocyte; TCR; γδ-T cell; mice
This is an open access article distributed under the Creative Commons Attribution License which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. (CC BY 4.0).

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MDPI and ACS Style

Huppler, A.R.; Verma, A.H.; Conti, H.R.; Gaffen, S.L. Neutrophils Do Not Express IL-17A in the Context of Acute Oropharyngeal Candidiasis. Pathogens 2015, 4, 559-572.

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