title: Neutrophils Do Not Express IL-17A in the Context of Acute Oropharyngeal Candidiasis.
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.
authors.affiliation: Children's Hospital of Pittsburgh of UPMC, Department of Pediatrics, Pittsburgh, PA 15224, USA. ahuppler@mcw.edu.|Medical College of Wisconsin, Department of Pediatrics, Division of Infectious Diseases, Milwaukee, WI 53201, USA. ahuppler@mcw.edu.
authors.forename: Anna R
authors.initials: AR
authors.lastname: Huppler
authors.affiliation: Department of Medicine, Division of Rheumatology & Clinical Immunology, University of Pittsburgh, BST S702, 200 Lothrop Street, Pittsburgh, PA 15261, USA. akash.verma@pitt.edu.
authors.forename: Akash H
authors.initials: AH
authors.lastname: Verma
authors.affiliation: Department of Medicine, Division of Rheumatology & Clinical Immunology, University of Pittsburgh, BST S702, 200 Lothrop Street, Pittsburgh, PA 15261, USA. hrc11@pitt.edu.
authors.forename: Heather R
authors.initials: HR
authors.lastname: Conti
authors.affiliation: Department of Medicine, Division of Rheumatology & Clinical Immunology, University of Pittsburgh, BST S702, 200 Lothrop Street, Pittsburgh, PA 15261, USA. sarah.gaffen@pitt.edu.
authors.forename: Sarah L
authors.initials: SL
authors.lastname: Gaffen
keywords: Candida albicans; IL-17; TCR; Th17; fungal infection; innate lymphocyte; mice; neutrophils; oral candidiasis; γδ-T cell