{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,10]],"date-time":"2026-10-10T19:22:28Z","timestamp":1791660148793,"version":"4.3.4"},"update-to":[{"DOI":"10.1371\/journal.ppat.1009405","type":"new_version","label":"New version","source":"publisher","updated":{"date-parts":[[2021,3,19]],"date-time":"2021-03-19T00:00:00Z","timestamp":1616112000000}}],"reference-count":47,"publisher":"Public Library of Science (PLoS)","issue":"3","license":[{"start":{"date-parts":[[2021,3,9]],"date-time":"2021-03-09T00:00:00Z","timestamp":1615248000000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/100000050","name":"National Heart, Lung, and Blood Institute","doi-asserted-by":"publisher","award":["R01 HL140496"],"award-info":[{"award-number":["R01 HL140496"]}],"id":[{"id":"10.13039\/100000050","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["www.plospathogens.org"],"crossmark-restriction":false},"short-container-title":["PLoS Pathog"],"abstract":"<jats:p>Bacterial co-infections represent a major clinical complication of influenza. Host-derived interferon (IFN) increases susceptibility to bacterial infections following influenza, but the relative roles of type-I versus type-II IFN remain poorly understood. We have used novel mouse models of co-infection in which colonizing pneumococci were inoculated into the upper respiratory tract; subsequent sublethal influenza virus infection caused the bacteria to enter the lungs and mediate lethal disease. Compared to wild-type mice or mice deficient in only one pathway, mice lacking both IFN pathways demonstrated the least amount of lung tissue damage and mortality following pneumococcal-influenza virus superinfection. Therapeutic neutralization of both type-I and type-II IFN pathways similarly provided optimal protection to co-infected wild-type mice. The most effective treatment regimen was staggered neutralization of the type-I IFN pathway early during co-infection combined with later neutralization of type-II IFN, which was consistent with the expression and reported activities of these IFNs during superinfection. These results are the first to directly compare the activities of type-I and type-II IFN during superinfection and provide new insights into potential host-directed targets for treatment of secondary bacterial infections during influenza.<\/jats:p>","DOI":"10.1371\/journal.ppat.1009405","type":"journal-article","created":{"date-parts":[[2021,3,9]],"date-time":"2021-03-09T13:33:46Z","timestamp":1615296826000},"page":"e1009405","update-policy":"https:\/\/doi.org\/10.1371\/journal.ppat.corrections_policy","source":"Crossref","is-referenced-by-count":26,"title":["Sequential targeting of interferon pathways for increased host resistance to bacterial superinfection during influenza"],"prefix":"10.1371","volume":"17","author":[{"given":"Tarani Kanta","family":"Barman","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rachael","family":"Racine","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jesse L.","family":"Bonin","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Danielle","family":"Califano","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sharon L.","family":"Salmon","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8000-9907","authenticated-orcid":true,"given":"Dennis W.","family":"Metzger","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"340","published-online":{"date-parts":[[2021,3,9]]},"reference":[{"issue":"3","key":"ppat.1009405.ref001","doi-asserted-by":"crossref","first-page":"432","DOI":"10.1093\/infdis\/jit190","article-title":"Bacterial complications of respiratory tract viral illness: a comprehensive evaluation","volume":"208","author":"AR Falsey","year":"2013","journal-title":"J Infect Dis"},{"issue":"7","key":"ppat.1009405.ref002","doi-asserted-by":"crossref","first-page":"962","DOI":"10.1086\/591708","article-title":"Predominant role of bacterial pneumonia as a cause of death in pandemic influenza: implications for pandemic influenza preparedness","volume":"198","author":"DM Morens","year":"2008","journal-title":"J Infect Dis"},{"issue":"2","key":"ppat.1009405.ref003","doi-asserted-by":"crossref","first-page":"235","DOI":"10.5858\/134.2.235","article-title":"Pulmonary pathologic findings of fatal 2009 pandemic influenza A\/H1N1 viral infections","volume":"134","author":"JR Gill","year":"2010","journal-title":"Arch Pathol Lab Med"},{"issue":"1 Part 2","key":"ppat.1009405.ref004","doi-asserted-by":"crossref","first-page":"213","DOI":"10.1172\/JCI103791","article-title":"Studies on influenza in the pandemic of 1957\u20131958. 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