{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,30]],"date-time":"2026-09-30T19:41:21Z","timestamp":1790797281360,"version":"4.1.0"},"reference-count":41,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2022,9,20]],"date-time":"2022-09-20T00:00:00Z","timestamp":1663632000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Immunol."],"abstract":"<jats:p>Acute Respiratory Distress Syndrome (ARDS) is an inflammatory disease that is associated with high mortality but no specific treatment. Our understanding of initial events that trigger ARDS pathogenesis is limited. We have developed a mouse model of inflammatory lung injury by influenza and methicillin-resistant <jats:italic>Staphylococcus aureus<\/jats:italic> (MRSA) coinfection plus daily antibiotic therapy. Using this pneumonic ARDS model, here we show that IFN-\u03b3 receptor signaling drives inflammatory cytokine storm and lung tissue damage. By single-cell RNA sequencing (scRNA-seq) analysis, we demonstrate that IFN-\u03b3 signaling induces a transcriptional shift in airway immune cells, particularly by upregulating macrophage and monocyte expression of genes associated with inflammatory diseases. Further evidence from conditional knockout mouse models reveals that IFN-\u03b3 receptor signaling in myeloid cells, particularly CD11c<jats:sup>+<\/jats:sup> mononuclear phagocytes, directly promotes TNF-\u03b1 hyperproduction and inflammatory lung damage. Collectively, the findings from this study, ranging from cell-intrinsic gene expression to overall disease outcome, demonstrate that influenza-induced IFN-\u03b3 triggers myeloid cell hyperresponsiveness to MRSA, thereby leading to excessive inflammatory response and lethal lung damage during coinfection.<\/jats:p>","DOI":"10.3389\/fimmu.2022.1011132","type":"journal-article","created":{"date-parts":[[2022,9,20]],"date-time":"2022-09-20T05:45:37Z","timestamp":1663652737000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":17,"title":["IFN-\u03b3 transforms the transcriptomic landscape and triggers myeloid cell hyperresponsiveness to cause lethal lung injury"],"prefix":"10.3389","volume":"13","author":[{"given":"Atul K.","family":"Verma","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Michael","family":"McKelvey","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Md Bashir","family":"Uddin","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sunil","family":"Palani","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Meng","family":"Niu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Christopher","family":"Bauer","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shengjun","family":"Shao","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Keer","family":"Sun","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2022,9,20]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","DOI":"10.1007\/s00134-020-06292-z","article-title":"Pulmonary infections complicating ARDS","volume":"46","author":"Luyt","year":"2020","journal-title":"Intensive Care Med"},{"key":"B2","doi-asserted-by":"publisher","DOI":"10.1007\/s00134-020-06299-6","article-title":"Current and evolving standards of care for patients with ARDS","volume":"46","author":"Menk","year":"2020","journal-title":"Intensive Care Med"},{"key":"B3","doi-asserted-by":"publisher","DOI":"10.1038\/s41591-020-1051-9","article-title":"An inflammatory cytokine signature predicts COVID-19 severity and survival","volume":"26","author":"Del Valle","year":"2020","journal-title":"Nat Med"},{"key":"B4","doi-asserted-by":"publisher","DOI":"10.1016\/j.bja.2020.12.017","article-title":"Association between inflammation, angiopoietins, and disease severity in critically ill COVID-19 patients: a prospective study","volume":"126","author":"Abou-Arab","year":"2021","journal-title":"Br J Anaesth"},{"key":"B5","doi-asserted-by":"publisher","DOI":"10.1086\/506430","article-title":"Acute respiratory distress syndrome and pneumonia: a comprehensive review of clinical data","volume":"43","author":"Bauer","year":"2006","journal-title":"Clin Infect Dis"},{"key":"B6","doi-asserted-by":"publisher","first-page":"18","DOI":"10.1038\/s41572-019-0069-0","article-title":"Acute respiratory distress syndrome","volume":"5","author":"Matthay","year":"2019","journal-title":"Nat Rev Dis Primers"},{"key":"B7","doi-asserted-by":"publisher","DOI":"10.1172\/JCI103791","article-title":"Studies on influenza in the pandemic of 1957-1958. 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