{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,23]],"date-time":"2026-09-23T03:16:09Z","timestamp":1790133369828,"version":"4.0.1"},"reference-count":48,"publisher":"Wiley","issue":"2","license":[{"start":{"date-parts":[[2026,3,25]],"date-time":"2026-03-25T00:00:00Z","timestamp":1774396800000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"},{"start":{"date-parts":[[2026,3,25]],"date-time":"2026-03-25T00:00:00Z","timestamp":1774396800000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["iMeta"],"published-print":{"date-parts":[[2026,4]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>\n                    Influenza A virus (IAV) infection has a wide clinical spectrum, from mild illness to life\u2010threatening pneumonia, yet the underlying immune determinants of disease remain poorly defined. Here, we generated a large\u2010scale single\u2010cell transcriptomic atlas from peripheral blood, profiling more than 612,010 cells from 97 individuals, including healthy controls, and patients with mild, severe, or convalescent IAV infection. Our findings uncovered a core immune dichotomy that determines clinical severity: a protective, monocyte\u2010centric antiviral state in mild disease versus a pathological, neutrophil\u2010 and myeloid\u2010derived suppressor cell (MDSC)\u2010driven hyperinflammatory state in severe infection. Severe disease was marked by a peripheral hyperinflammatory state, driven by specific monocyte and neutrophil subsets via the\n                    <jats:italic>S100A8<\/jats:italic>\n                    \/\n                    <jats:italic>9<\/jats:italic>\n                    \/12\u2013\n                    <jats:italic>TLR4<\/jats:italic>\n                    \/\n                    <jats:italic>RAGE<\/jats:italic>\n                    signaling axis, and was coupled with the expansion of granulocytic MDSCs that likely contribute to T cell paralysis. In contrast, mild disease was associated with a protective, monocyte\u2010centric response characterized by robust antiviral interferon signaling and enhanced antigen presentation. This functional divergence extends to the adaptive immune system, where mild disease was associated with CD8\n                    <jats:sup>+<\/jats:sup>\n                    T cells displaying a balance of high cytotoxicity and regulated exhaustion. In severe illness, however, T cells become profoundly dysfunctional, exhibiting signatures of metabolic stress and apoptosis alongside the emergence of pathogenic, pro\u2010inflammatory regulatory T cells. Together, our atlas provides a high\u2010resolution immunological blueprint of human IAV infection, delineates the cellular states and pathways that govern clinical trajectories and offers a critical resource for developing host\u2010directed therapies.\n                  <\/jats:p>","DOI":"10.1002\/imt2.70121","type":"journal-article","created":{"date-parts":[[2026,3,26]],"date-time":"2026-03-26T04:02:26Z","timestamp":1774497746000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":2,"title":["A large\u2010scale single\u2010cell transcriptomic atlas indicates the immune panorama of influenza A infection"],"prefix":"10.1002","volume":"5","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-2031-087X","authenticated-orcid":false,"given":"Yi","family":"Wang","sequence":"first","affiliation":[{"name":"Experimental Research Center &amp; Molecular Diagnostic Center, Capital Center for Children's Health Capital Medical University, Capital Institute of Pediatrics Beijing China"},{"name":"Beijing Research Center for Respiratory Infectious Diseases Beijing China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shuzi","family":"Liu","sequence":"additional","affiliation":[{"name":"Department of Respiratory and Critical Care Medicine, The Eight Medical Center Chinese PLA General Hospital Beijing China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Laurence Don Wai","family":"Luu","sequence":"additional","affiliation":[{"name":"School of Biotechnology and Biomolecular Sciences, University of New South Wales Sydney Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yongzhi","family":"Zhai","sequence":"additional","affiliation":[{"name":"Department of Emergency, The First Medical Center Chinese PLA General Hospital, Medical School of Chinese PLA Beijing China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chenliang","family":"Zhu","sequence":"additional","affiliation":[{"name":"Department of Clinical Laboratory, Institute of Translational Medicine Renmin Hospital of Wuhan University Wuhan China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zhaomin","family":"Feng","sequence":"additional","affiliation":[{"name":"Beijing Key Laboratory of Surveillance, Early Warning and Pathogen Research on Emerging Infectious Diseases, Beijing Research Center for Respiratory Infectious Diseases, Beijing Center for Disease Prevention and Control Beijing China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yao","family":"Tan","sequence":"additional","affiliation":[{"name":"College of Pulmonary and Critical Care Medicine, Chinese PLA General Hospital Beijing 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