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However, uncontrolled inflammation and the \u201ccytokine storm\u201d are hallmarks of immunopathology in severe infection. Cytokine storm is a broad term for a phenomenon with diverse characteristics and drivers, depending on host genetics, age, and other factors. Taking advantage of the differential use of virus-sensing systems by different cell types, we test the hypothesis that specifically blocking TLR7-dependent, immune cell\u2013produced cytokines reduces influenza-related immunopathology. In a mouse model of severe influenza characterized by a type I interferon (IFN-I)\u2013driven cytokine storm, TLR7 antagonist treatment leaves epithelial antiviral responses unaltered but acts through pDCs and monocytes to reduce IFN-I and other cytokines in the lung, thus ameliorating inflammation and severity. Moreover, even in the absence of IFN-I signaling, TLR7 antagonism reduces inflammation and mortality driven by monocyte-produced chemoattractants and neutrophil recruitment into the infected lung. Hence, TLR7 antagonism reduces diverse types of cytokine storm in severe influenza.<\/jats:p>","DOI":"10.1084\/jem.20201631","type":"journal-article","created":{"date-parts":[[2021,8,17]],"date-time":"2021-08-17T02:21:29Z","timestamp":1629166889000},"update-policy":"https:\/\/doi.org\/10.1084\/jem.crossmarkpolicy","source":"Crossref","is-referenced-by-count":36,"title":["A TLR7 antagonist restricts interferon-dependent and -independent immunopathology in a mouse model of severe influenza"],"prefix":"10.1084","volume":"218","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-9230-0219","authenticated-orcid":true,"given":"Julie C.F.","family":"Rappe","sequence":"first","affiliation":[{"name":"Immunoregulation Laboratory, Francis Crick Institute, London, UK 1"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3596-4240","authenticated-orcid":true,"given":"Katja","family":"Finsterbusch","sequence":"additional","affiliation":[{"name":"Immunoregulation Laboratory, Francis Crick Institute, London, UK 1"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4676-8616","authenticated-orcid":true,"given":"Stefania","family":"Crotta","sequence":"additional","affiliation":[{"name":"Immunoregulation Laboratory, Francis Crick Institute, London, UK 1"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3157-7262","authenticated-orcid":true,"given":"Matthias","family":"Mack","sequence":"additional","affiliation":[{"name":"Department of Nephrology, University Hospital Regensburg, Regensburg, Germany 2"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6027-1879","authenticated-orcid":true,"given":"Simon L.","family":"Priestnall","sequence":"additional","affiliation":[{"name":"Department of Pathobiology and Population Sciences, The Royal Veterinary College, Hatfield, UK 3"},{"name":"Experimental Histopathology Science Technology Platform, The Francis Crick Institute, London, UK 4"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5226-2991","authenticated-orcid":true,"given":"Andreas","family":"Wack","sequence":"additional","affiliation":[{"name":"Immunoregulation Laboratory, Francis Crick Institute, London, UK 1"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"291","published-online":{"date-parts":[[2021,9,2]]},"reference":[{"key":"2023072610071824300_bib1","doi-asserted-by":"publisher","first-page":"4791","DOI":"10.4049\/jimmunol.1600672","article-title":"Characterization and transcriptomic analysis of porcine blood conventional and plasmacytoid dendritic cells reveals striking species-specific differences","volume":"197","author":"Auray","year":"2016","journal-title":"J. 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