{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,30]],"date-time":"2026-09-30T14:58:44Z","timestamp":1790780324701,"version":"4.1.0"},"update-to":[{"DOI":"10.1371\/journal.ppat.1011847","type":"new_version","label":"New version","source":"publisher","updated":{"date-parts":[[2023,12,19]],"date-time":"2023-12-19T00:00:00Z","timestamp":1702944000000}}],"reference-count":46,"publisher":"Public Library of Science (PLoS)","issue":"12","license":[{"start":{"date-parts":[[2023,12,7]],"date-time":"2023-12-07T00:00:00Z","timestamp":1701907200000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/100000009","name":"Foundation for the National Institutes of Health","doi-asserted-by":"publisher","award":["R01 AI143741"],"award-info":[{"award-number":["R01 AI143741"]}],"id":[{"id":"10.13039\/100000009","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000009","name":"Foundation for the National Institutes of Health","doi-asserted-by":"publisher","award":["R21 AI151522"],"award-info":[{"award-number":["R21 AI151522"]}],"id":[{"id":"10.13039\/100000009","id-type":"DOI","asserted-by":"publisher"}]},{"name":"National Institute of Centers of Biomedical Research Excellence","award":["5P20GM113123"],"award-info":[{"award-number":["5P20GM113123"]}]},{"name":"IDeA Network of Biomedical Research Excellence","award":["5P20GM103442"],"award-info":[{"award-number":["5P20GM103442"]}]},{"DOI":"10.13039\/100000057","name":"National Institute of General Medical Sciences","doi-asserted-by":"publisher","award":["P20GM113123"],"award-info":[{"award-number":["P20GM113123"]}],"id":[{"id":"10.13039\/100000057","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000057","name":"National Institute of General Medical Sciences","doi-asserted-by":"publisher","award":["U54GM128729"],"award-info":[{"award-number":["U54GM128729"]}],"id":[{"id":"10.13039\/100000057","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["www.plospathogens.org"],"crossmark-restriction":false},"short-container-title":["PLoS Pathog"],"abstract":"<jats:p>The upper respiratory tract (nasopharynx or NP) is the first site of influenza replication, allowing the virus to disseminate to the lower respiratory tract or promoting community transmission. The host response in the NP regulates an intricate balance between viral control and tissue pathology. The hyper-inflammatory responses promote epithelial injury, allowing for increased viral dissemination and susceptibility to secondary bacterial infections. However, the pathologic contributors to influenza upper respiratory tissue pathology are incompletely understood. In this study, we investigated the role of interleukin IL-17 recetor A (IL-17RA) as a modulator of influenza host response and inflammation in the upper respiratory tract. We used a combined experimental approach involving IL-17RA<jats:sup>-\/-<\/jats:sup> mice and an air-liquid interface (ALI) epithelial culture model to investigate the role of IL-17 response in epithelial inflammation, barrier function, and tissue pathology. Our data show that IL-17RA<jats:sup>-\/-<\/jats:sup> mice exhibited significantly reduced neutrophilia, epithelial injury, and viral load. The reduced NP inflammation and epithelial injury in IL-17RA<jats:sup>-\/-<\/jats:sup> mice correlated with increased resistance against co-infection by <jats:italic>Streptococcus pneumoniae (Spn)<\/jats:italic>. IL-17A treatment, while potentiating the apoptosis of IAV-infected epithelial cells, caused bystander cell death and disrupted the barrier function in ALI epithelial model, supporting the <jats:italic>in vivo<\/jats:italic> findings.<\/jats:p>","DOI":"10.1371\/journal.ppat.1011847","type":"journal-article","created":{"date-parts":[[2023,12,7]],"date-time":"2023-12-07T18:47:27Z","timestamp":1701974847000},"page":"e1011847","update-policy":"https:\/\/doi.org\/10.1371\/journal.ppat.corrections_policy","source":"Crossref","is-referenced-by-count":9,"title":["IL-17RA promotes pathologic epithelial inflammation in a mouse model of upper respiratory influenza infection"],"prefix":"10.1371","volume":"19","author":[{"given":"Zahrasadat","family":"Navaeiseddighi","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jitendra 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