{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,5,18]],"date-time":"2026-05-18T22:16:40Z","timestamp":1779142600702,"version":"3.51.4"},"reference-count":49,"publisher":"American Society for Clinical Investigation","issue":"10","license":[{"start":{"date-parts":[[2023,5,22]],"date-time":"2023-05-22T00:00:00Z","timestamp":1684713600000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"crossref","award":["HL102371,HL153113,HL105346,HL148514-01"],"award-info":[{"award-number":["HL102371,HL153113,HL105346,HL148514-01"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"crossref"}]},{"DOI":"10.13039\/100000897","name":"Cystic Fibrosis Foundation","doi-asserted-by":"crossref","award":["ROWE19R0,HARROD20G0,MARGAR21F5"],"award-info":[{"award-number":["ROWE19R0,HARROD20G0,MARGAR21F5"]}],"id":[{"id":"10.13039\/100000897","id-type":"DOI","asserted-by":"crossref"}]},{"DOI":"10.13039\/100000738","name":"U.S. Department of Veterans Affairs","doi-asserted-by":"crossref","award":["1I01CX001969"],"award-info":[{"award-number":["1I01CX001969"]}],"id":[{"id":"10.13039\/100000738","id-type":"DOI","asserted-by":"crossref"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2023,5,22]]},"abstract":"<jats:p>\n                    Neutrophilic inflammation characterizes several respiratory viral infections, including COVID-19\u2013related acute respiratory distress syndrome, although its contribution to disease pathogenesis remains poorly understood. Blood and airway immune cells from 52 patients with severe COVID-19 were phenotyped by flow cytometry. Samples and clinical data were collected at 2 separate time points to assess changes during ICU stay. Blockade of type I interferon and interferon-induced protein with tetratricopeptide repeats 3 (IFIT3) signaling was performed in vitro to determine their contribution to viral clearance in A2 neutrophils. We identified 2 neutrophil subpopulations (A1 and A2) in the airway compartment, where loss of the A2 subset correlated with increased viral burden and reduced 30-day survival. A2 neutrophils exhibited a discrete antiviral response with an increased interferon signature. Blockade of type I interferon attenuated viral clearance in A2 neutrophils and downregulated\n                    <jats:italic>IFIT3<\/jats:italic>\n                    and key catabolic genes, demonstrating direct antiviral neutrophil function. Knockdown of\n                    <jats:italic>IFIT3<\/jats:italic>\n                    in A2 neutrophils led to loss of IRF3 phosphorylation, with consequent reduced viral catabolism, providing the first discrete mechanism to our knowledge of type I interferon signaling in neutrophils. The identification of this neutrophil phenotype and its association with severe COVID-19 outcomes emphasizes its likely importance in other respiratory viral infections and potential for new therapeutic approaches in viral illness.\n                  <\/jats:p>","DOI":"10.1172\/jci.insight.167042","type":"journal-article","created":{"date-parts":[[2023,4,18]],"date-time":"2023-04-18T12:03:29Z","timestamp":1681819409000},"source":"Crossref","is-referenced-by-count":11,"title":["Interferon-dependent signaling is critical for viral clearance in airway neutrophils"],"prefix":"10.1172","volume":"8","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-3952-0778","authenticated-orcid":true,"given":"Camilla","family":"Margaroli","sequence":"first","affiliation":[{"name":"Department of Medicine, Division of Pulmonary, Allergy and Critical Care Medicine,"},{"name":"Program in Protease and Matrix Biology,"},{"name":"Department of Pathology, Division of Molecular and Cellular Pathology, 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