{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,2]],"date-time":"2026-10-02T14:30:10Z","timestamp":1790951410319,"version":"4.1.0"},"reference-count":64,"publisher":"American Association for the Advancement of Science (AAAS)","issue":"6775","content-domain":{"domain":["www.science.org"],"crossmark-restriction":true},"short-container-title":["Science"],"published-print":{"date-parts":[[2025,11,20]]},"abstract":"<jats:p>\n                    Maintaining tissue function while eliminating infected cells is fundamental, and inflammatory damage plays a major contribution to lethality after lung infection. We tested 50 immunomodulatory regimes to determine their ability to protect mice from lethal infection. Only neutrophil depletion soon after infection prevented death from influenza. This result suggests that the infected host passed an early tipping point after which limiting innate damage alone could not rescue lung function. We investigated treatments that could have efficacy when administered later in infection. We found that partial limitation of viral spread together with enhancement of epithelial repair, by interferon blockade or limiting CD8\n                    <jats:sup>+<\/jats:sup>\n                    T cell\u2013mediated killing of epithelial cells, reduced lethality. This finding highlights the importance of rebalancing repair and damage processes in the survival of pulmonary infections.\n                  <\/jats:p>","DOI":"10.1126\/science.adr4635","type":"journal-article","created":{"date-parts":[[2025,11,20]],"date-time":"2025-11-20T19:02:32Z","timestamp":1763665352000},"update-policy":"https:\/\/doi.org\/10.34133\/aaas_crossmark","source":"Crossref","is-referenced-by-count":11,"title":["Rebalancing viral and immune damage versus repair prevents death from lethal influenza infection"],"prefix":"10.1126","volume":"390","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-5187-810X","authenticated-orcid":true,"given":"Hiroshi","family":"Ichise","sequence":"first","affiliation":[{"name":"Lymphocyte Biology Section, Laboratory of Immune System Biology, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0666-4804","authenticated-orcid":true,"given":"Emily","family":"Speranza","sequence":"additional","affiliation":[{"name":"Florida Research and Innovation Center, Cleveland Clinic Lerner Research Institute, Port Saint Lucie, FL, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1885-6566","authenticated-orcid":true,"given":"Federica","family":"La Russa","sequence":"additional","affiliation":[{"name":"Lymphocyte Biology Section, Laboratory of Immune System Biology, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6980-8900","authenticated-orcid":true,"given":"Tibor Z.","family":"Veres","sequence":"additional","affiliation":[{"name":"Lymphocyte Biology Section, Laboratory of Immune System Biology, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2088-8310","authenticated-orcid":true,"given":"Colin J.","family":"Chu","sequence":"additional","affiliation":[{"name":"UCL Institute of Ophthalmology, University College London, London, UK."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Anita","family":"Gola","sequence":"additional","affiliation":[{"name":"Lymphocyte Biology Section, Laboratory of Immune System Biology, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0003-9817-7874","authenticated-orcid":true,"given":"Beatrice H.","family":"Clark","sequence":"additional","affiliation":[{"name":"Lymphocyte Biology Section, Laboratory of Immune System Biology, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1495-9143","authenticated-orcid":true,"given":"Ronald N.","family":"Germain","sequence":"additional","affiliation":[{"name":"Lymphocyte Biology Section, Laboratory of Immune System Biology, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD, USA."},{"name":"Center for Advanced Tissue Imaging, Laboratory of Immune System Biology, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"221","reference":[{"key":"e_1_3_2_2_2","unstructured":"World Health Organization Influenza (seasonal); https:\/\/www.who.int\/news-room\/fact-sheets\/detail\/influenza-(seasonal)."},{"key":"e_1_3_2_3_2","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMp0904819"},{"key":"e_1_3_2_4_2","doi-asserted-by":"publisher","DOI":"10.1353\/bhm.2002.0022"},{"key":"e_1_3_2_5_2","doi-asserted-by":"publisher","DOI":"10.1146\/annurev.pathmechdis.3.121806.154316"},{"key":"e_1_3_2_6_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.cell.2013.06.013"},{"key":"e_1_3_2_7_2","doi-asserted-by":"publisher","DOI":"10.1038\/ncomms4864"},{"key":"e_1_3_2_8_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.cell.2011.08.015"},{"key":"e_1_3_2_9_2","doi-asserted-by":"publisher","DOI":"10.4049\/jimmunol.180.4.2562"},{"key":"e_1_3_2_10_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.ajpath.2011.03.013"},{"key":"e_1_3_2_11_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.coviro.2012.04.004"},{"key":"e_1_3_2_12_2","doi-asserted-by":"publisher","DOI":"10.3389\/fimmu.2020.01022"},{"key":"e_1_3_2_13_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.chom.2021.05.004"},{"key":"e_1_3_2_14_2","doi-asserted-by":"publisher","DOI":"10.1007\/s00281-017-0629-x"},{"key":"e_1_3_2_15_2","doi-asserted-by":"publisher","DOI":"10.3389\/fimmu.2015.00361"},{"key":"e_1_3_2_16_2","unstructured":"Centers for Disease Control and Prevention Influenza Antiviral Medications: Summary for Clinicians; https:\/\/www.cdc.gov\/flu\/hcp\/antivirals\/summary-clinicians.html."},{"key":"e_1_3_2_17_2","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa2021436"},{"key":"e_1_3_2_18_2","doi-asserted-by":"publisher","DOI":"10.3389\/fmed.2022.921452"},{"key":"e_1_3_2_19_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.chom.2016.01.007"},{"key":"e_1_3_2_20_2","doi-asserted-by":"publisher","DOI":"10.1183\/09031936.00186214"},{"key":"e_1_3_2_21_2","doi-asserted-by":"publisher","DOI":"10.1038\/s41467-020-16596-9"},{"key":"e_1_3_2_22_2","doi-asserted-by":"publisher","DOI":"10.1126\/sciimmunol.ado1227"},{"key":"e_1_3_2_23_2","doi-asserted-by":"publisher","DOI":"10.1172\/JCI45961"},{"key":"e_1_3_2_24_2","doi-asserted-by":"publisher","DOI":"10.1038\/jid.2013.164"},{"key":"e_1_3_2_25_2","doi-asserted-by":"publisher","DOI":"10.1172\/JCI68782"},{"key":"e_1_3_2_26_2","doi-asserted-by":"publisher","DOI":"10.1038\/s41586-021-03570-8"},{"key":"e_1_3_2_27_2","doi-asserted-by":"publisher","DOI":"10.1126\/science.abc2061"},{"key":"e_1_3_2_28_2","first-page":"35","article-title":"The type 2 cell as progenitor of alveolar epithelial regeneration. A cytodynamic study in mice after exposure to oxygen","volume":"30","author":"Adamson I. Y.","year":"1974","unstructured":"I. Y. Adamson, D. H. Bowden, The type 2 cell as progenitor of alveolar epithelial regeneration. A cytodynamic study in mice after exposure to oxygen. Lab. Invest. 30, 35\u201342 (1974). 4812806","journal-title":"Lab. Invest."},{"key":"e_1_3_2_29_2","doi-asserted-by":"publisher","DOI":"10.1038\/nature25786"},{"key":"e_1_3_2_30_2","doi-asserted-by":"publisher","DOI":"10.1126\/science.aam6603"},{"key":"e_1_3_2_31_2","doi-asserted-by":"publisher","DOI":"10.3389\/fpubh.2022.1029190"},{"key":"e_1_3_2_32_2","doi-asserted-by":"publisher","DOI":"10.1038\/s41586-020-2700-3"},{"key":"e_1_3_2_33_2","doi-asserted-by":"publisher","DOI":"10.1172\/jci.insight.162041"},{"key":"e_1_3_2_34_2","doi-asserted-by":"publisher","DOI":"10.1038\/s41556-020-0569-x"},{"key":"e_1_3_2_35_2","doi-asserted-by":"publisher","DOI":"10.1038\/nature14984"},{"key":"e_1_3_2_36_2","doi-asserted-by":"publisher","DOI":"10.1038\/nri3787"},{"key":"e_1_3_2_37_2","doi-asserted-by":"publisher","DOI":"10.1089\/jir.2014.0227"},{"key":"e_1_3_2_38_2","doi-asserted-by":"publisher","DOI":"10.1172\/JCI126363"},{"key":"e_1_3_2_39_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.chom.2020.07.005"},{"key":"e_1_3_2_40_2","doi-asserted-by":"publisher","DOI":"10.1038\/nature14112"},{"key":"e_1_3_2_41_2","doi-asserted-by":"publisher","DOI":"10.1038\/nature13903"},{"key":"e_1_3_2_42_2","doi-asserted-by":"publisher","DOI":"10.1172\/JCI170498"},{"key":"e_1_3_2_43_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.immuni.2021.05.010"},{"key":"e_1_3_2_44_2","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa2028700"},{"key":"e_1_3_2_45_2","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa2101643"},{"key":"e_1_3_2_46_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.jaci.2020.05.019"},{"key":"e_1_3_2_47_2","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa2100433"},{"key":"e_1_3_2_48_2","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa2028836"},{"key":"e_1_3_2_49_2","doi-asserted-by":"publisher","DOI":"10.1126\/science.80.2081.457.b"},{"key":"e_1_3_2_50_2","doi-asserted-by":"publisher","DOI":"10.1084\/jem.62.4.505"},{"key":"e_1_3_2_51_2","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.2018488117"},{"key":"e_1_3_2_52_2","doi-asserted-by":"publisher","DOI":"10.1038\/s41596-021-00644-9"},{"key":"e_1_3_2_53_2","doi-asserted-by":"publisher","DOI":"10.1038\/s41592-020-01018-x"},{"key":"e_1_3_2_54_2","doi-asserted-by":"publisher","DOI":"10.1038\/s41592-022-01663-4"},{"key":"e_1_3_2_55_2","doi-asserted-by":"publisher","DOI":"10.1093\/bioinformatics\/btt276"},{"key":"e_1_3_2_56_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.immuni.2012.07.011"},{"key":"e_1_3_2_57_2","doi-asserted-by":"publisher","DOI":"10.1093\/bioinformatics\/bts635"},{"key":"e_1_3_2_58_2","doi-asserted-by":"publisher","DOI":"10.1093\/bioinformatics\/btt656"},{"key":"e_1_3_2_59_2","doi-asserted-by":"publisher","DOI":"10.1093\/bioinformatics\/btp616"},{"key":"e_1_3_2_60_2","doi-asserted-by":"crossref","unstructured":"G. Korotkevich V. Sukhov N. Budin B. Shpak M. N. Artyomov A. Sergushichev Fast gene set enrichment analysis. bioRxiv 060012 [Preprint] (2021); https:\/\/doi.org\/10.1101\/060012.","DOI":"10.1101\/060012"},{"key":"e_1_3_2_61_2","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.0506580102"},{"key":"e_1_3_2_62_2","doi-asserted-by":"publisher","DOI":"10.1038\/s41467-018-08023-x"},{"key":"e_1_3_2_63_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.isci.2021.103025"},{"key":"e_1_3_2_64_2","first-page":"E7321","article-title":"Multiplex, quantitative cellular analysis in large tissue volumes with clearing-enhanced 3D microscopy (Ce3D)","volume":"114","author":"Li W.","year":"2017","unstructured":"W. Li, R. N. Germain, M. Y. Gerner, Multiplex, quantitative cellular analysis in large tissue volumes with clearing-enhanced 3D microscopy (Ce3D). Proc. Natl. Acad. Sci. U.S.A. 114, E7321\u2013E7330 (2017). 28808033","journal-title":"Proc. Natl. Acad. Sci. U.S.A."},{"key":"e_1_3_2_65_2","doi-asserted-by":"publisher","DOI":"10.2119\/molmed.2010.00264"}],"container-title":["Science"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.science.org\/doi\/pdf\/10.1126\/science.adr4635","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,11,20]],"date-time":"2025-11-20T19:02:39Z","timestamp":1763665359000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.science.org\/doi\/10.1126\/science.adr4635"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2025,11,20]]},"references-count":64,"journal-issue":{"issue":"6775","published-print":{"date-parts":[[2025,11,20]]}},"alternative-id":["10.1126\/science.adr4635"],"URL":"https:\/\/doi.org\/10.1126\/science.adr4635","relation":{"has-preprint":[{"id-type":"doi","id":"10.1101\/2024.07.04.601620","asserted-by":"object"}]},"ISSN":["0036-8075","1095-9203"],"issn-type":[{"value":"0036-8075","type":"print"},{"value":"1095-9203","type":"electronic"}],"subject":[],"published":{"date-parts":[[2025,11,20]]},"assertion":[{"value":"2024-07-02","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2025-04-21","order":1,"name":"revised","label":"Revised","group":{"name":"publication_history","label":"Publication History"}},{"value":"2025-08-14","order":2,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2025-11-20","order":3,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}],"article-number":"eadr4635"}}