{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,29]],"date-time":"2026-09-29T11:18:54Z","timestamp":1790680734070,"version":"4.1.0"},"reference-count":234,"publisher":"MDPI AG","issue":"12","license":[{"start":{"date-parts":[[2021,12,15]],"date-time":"2021-12-15T00:00:00Z","timestamp":1639526400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100001280","name":"Horserace Betting Levy Board","doi-asserted-by":"publisher","award":["VET\/2020 -1 EPDF 7"],"award-info":[{"award-number":["VET\/2020 -1 EPDF 7"]}],"id":[{"id":"10.13039\/501100001280","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Viruses"],"abstract":"<jats:p>Influenza A viruses (IAVs) are important respiratory pathogens of horses and humans. Infected individuals develop typical respiratory disorders associated with the death of airway epithelial cells (AECs) in infected areas. Virulence and risk of secondary bacterial infections vary among IAV strains. The IAV non-structural proteins, NS1, PB1-F2, and PA-X are important virulence factors controlling AEC death and host immune responses to viral and bacterial infection. Polymorphism in these proteins impacts their function. Evidence from human and mouse studies indicates that upon IAV infection, the manner of AEC death impacts disease severity. Indeed, while apoptosis is considered anti-inflammatory, necrosis is thought to cause pulmonary damage with the release of damage-associated molecular patterns (DAMPs), such as interleukin-33 (IL-33). IL-33 is a potent inflammatory mediator released by necrotic cells, playing a crucial role in anti-viral and anti-bacterial immunity. Here, we discuss studies in human and murine models which investigate how viral determinants and host immune responses control AEC death and subsequent lung IL-33 release, impacting IAV disease severity. Confirming such data in horses and improving our understanding of early immunologic responses initiated by AEC death during IAV infection will better inform the development of novel therapeutic or vaccine strategies designed to protect life-long lung health in horses and humans, following a One Health approach.<\/jats:p>","DOI":"10.3390\/v13122519","type":"journal-article","created":{"date-parts":[[2021,12,15]],"date-time":"2021-12-15T21:47:36Z","timestamp":1639604856000},"page":"2519","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":5,"title":["Could Interleukin-33 (IL-33) Govern the Outcome of an Equine Influenza Virus Infection? Learning from Other Species"],"prefix":"10.3390","volume":"13","author":[{"given":"Christoforos","family":"Rozario","sequence":"first","affiliation":[{"name":"Centre for Inflammation Research, The Queen\u2019s Medical Research Institute, The University of Edinburgh, Edinburgh BioQuarter, Edinburgh EH16 4TJ, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7084-0804","authenticated-orcid":false,"given":"Luis","family":"Mart\u00ednez-Sobrido","sequence":"additional","affiliation":[{"name":"Texas Biomedical Research Institute, San Antonio, TX 78227, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Henry J.","family":"McSorley","sequence":"additional","affiliation":[{"name":"Division of Cell Signalling and Immunology, School of Life Sciences, University of Dundee, Wellcome Trust Building, Dow Street, Dundee DD1 5EH, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9127-4693","authenticated-orcid":false,"given":"Caroline","family":"Chauch\u00e9","sequence":"additional","affiliation":[{"name":"Centre for Inflammation Research, The Queen\u2019s Medical Research Institute, The University of Edinburgh, Edinburgh BioQuarter, Edinburgh EH16 4TJ, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2021,12,15]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"205","DOI":"10.1016\/0147-9571(96)00006-9","article-title":"Equine Influenza","volume":"19","author":"Timoney","year":"1996","journal-title":"Comp. 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