{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,3,4]],"date-time":"2026-03-04T05:10:06Z","timestamp":1772601006140,"version":"3.50.1"},"reference-count":36,"publisher":"Oxford University Press (OUP)","issue":"1","license":[{"start":{"date-parts":[[2025,1,23]],"date-time":"2025-01-23T00:00:00Z","timestamp":1737590400000},"content-version":"vor","delay-in-days":22,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"publisher","award":["HL107380"],"award-info":[{"award-number":["HL107380"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"publisher","award":["HL146479"],"award-info":[{"award-number":["HL146479"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2025,1,23]]},"abstract":"<jats:title>Abstract<\/jats:title>\n               <jats:p>Influenza virus infects millions each year, contributing greatly to human morbidity and mortality. Upon viral infection, pathogen-associated molecular patterns activate pattern recognition receptors on host cells, triggering an immune response. The CD209 protein family, homologs of DC-SIGN (dendritic cell\u2013specific intercellular adhesion molecule 3\u2013grabbing nonintegrin), is thought to modulate immune responses to viruses. The effects of the mouse functional DC-SIGN homolog CD209d\/e on the lung immune responses during influenza viral infection are not known. Therefore, we generated mice that lack both CD209d and e isoforms to determine the role in influenza viral infection. We infected wild-type and CD209d\/e gene\u2013deficient (CD209d\/e\u2212\/\u2212) mice with influenza virus and measured the cellular response in bronchoalveolar lavage, the expression of proinflammatory cytokines, antiviral genes, toll-like receptors (TLRs) in the lung, and lung pathology. We found CD209d\/e\u2212\/\u2212 mice had decreased viral burden, TLR3 and TLR9 expression, interferon response, macrophages in bronchoalveolar lavage, and parenchymal lung inflammation compared with control mice. We also found less influenza viral uptake in alveolar macrophages and bone marrow\u2013derived macrophages isolated from CD209d\/e\u2212\/\u2212 mice when compared with control mice. We further investigated the role CD209d\/e by treating bone marrow\u2013derived macrophages from control and CD209d\/e\u2212\/\u2212 mice with TLR agonists. We found that lacking CD209d\/e decreased the expression of TLR3, TLR9, RIG1, STAT1, and STAT2 compared with controls. Collectively these results show that CD209d\/e plays an important role in viral sensing\/uptake and inflammatory immune responses during influenza viral infection.<\/jats:p>","DOI":"10.1093\/immhor\/vlae001","type":"journal-article","created":{"date-parts":[[2025,1,23]],"date-time":"2025-01-23T15:00:06Z","timestamp":1737644406000},"source":"Crossref","is-referenced-by-count":1,"title":["CD209d\/e promotes inflammation and lung injury during influenza virus infection"],"prefix":"10.1093","volume":"9","author":[{"given":"Radha","family":"Gopal","sequence":"first","affiliation":[{"name":"Division of Pulmonary Medicine, Department of Pediatrics, UPMC Children\u2019s Hospital of Pittsburgh , Pittsburgh, PA,","place":["United States"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Michael A","family":"Marinelli","sequence":"additional","affiliation":[{"name":"Division of Pulmonary Medicine, Department of Pediatrics, UPMC Children\u2019s Hospital of Pittsburgh , Pittsburgh, PA,","place":["United States"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0009-0003-1291-060X","authenticated-orcid":false,"given":"Flavia","family":"Rago","sequence":"additional","affiliation":[{"name":"Division of Pulmonary Medicine, Department of Pediatrics, UPMC Children\u2019s Hospital of Pittsburgh , Pittsburgh, PA,","place":["United States"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0009-0002-4167-9497","authenticated-orcid":false,"given":"Lacee J","family":"Richwalls","sequence":"additional","affiliation":[{"name":"Division of Pulmonary Medicine, Department of Pediatrics, UPMC Children\u2019s Hospital of Pittsburgh , Pittsburgh, PA,","place":["United States"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0009-0007-1102-8251","authenticated-orcid":false,"given":"Nicholas J","family":"Constantinesco","sequence":"additional","affiliation":[{"name":"Division of Pulmonary Medicine, Department of Pediatrics, UPMC Children\u2019s Hospital of Pittsburgh , Pittsburgh, PA,","place":["United States"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Deepa","family":"Debnath","sequence":"additional","affiliation":[{"name":"Division of Pulmonary Medicine, Department of Pediatrics, UPMC Children\u2019s Hospital of Pittsburgh , Pittsburgh, PA,","place":["United States"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3385-4558","authenticated-orcid":false,"given":"Saran","family":"Kupul","sequence":"additional","affiliation":[{"name":"Division of Pulmonary Medicine, Department of Pediatrics, UPMC Children\u2019s Hospital of Pittsburgh , Pittsburgh, PA,","place":["United States"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Maria de la Luz","family":"Garcia-Hernandez","sequence":"additional","affiliation":[{"name":"Division of Allergy, Immunology and Rheumatology, Department of Medicine, University of Rochester , Rochester, NY,","place":["United States"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9738-1182","authenticated-orcid":false,"given":"Javier","family":"Rangel-Moreno","sequence":"additional","affiliation":[{"name":"Division of Allergy, Immunology and Rheumatology, Department of Medicine, University of Rochester , Rochester, NY,","place":["United States"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5151-6304","authenticated-orcid":false,"given":"Jay K","family":"Kolls","sequence":"additional","affiliation":[{"name":"Center for Translational Research in Infection and Inflammation, Tulane University School of Medicine , New Orleans, LA,","place":["United States"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5997-7711","authenticated-orcid":false,"given":"John 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