{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,13]],"date-time":"2026-10-13T02:42:30Z","timestamp":1791859350425,"version":"4.3.4"},"reference-count":45,"publisher":"Oxford University Press (OUP)","issue":"12","license":[{"start":{"date-parts":[[2024,11,1]],"date-time":"2024-11-01T00:00:00Z","timestamp":1730419200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/academic.oup.com\/pages\/standard-publication-reuse-rights"}],"funder":[{"DOI":"10.13039\/100000050","name":"HHS | NIH | National Heart, Lung, and Blood Institute","doi-asserted-by":"publisher","award":["HL107380"],"award-info":[{"award-number":["HL107380"]}],"id":[{"id":"10.13039\/100000050","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2024,12,15]]},"abstract":"<jats:title>Abstract<\/jats:title>\n               <jats:p>Every year millions of people are infected with influenza, which can be complicated by secondary bacterial pneumonia. One factor that may contribute to increased susceptibility to secondary bacterial infection is the modulation of inflammatory cytokines. NF erythroid 2\u2013related factor 2 (Nrf2) has been shown to be a master regulator of the antioxidant response and various inflammatory cytokines. To test the role of Nrf2 during viral\u2013bacterial superinfection, we used a mouse model of influenza\u2013Staphylococcus aureus superinfection with wild-type (WT) or Nrf2-deficient (Nrf2\u2212\/\u2212) mice. Loss of Nrf2 reduced influenza burden and increased S. aureus burden during superinfection. Additionally, Nrf2\u2212\/\u2212 mice had increased abundance of conventional type 1 dendritic cells (DCs). We then tested the interaction between DCs and T cells using an in vitro model of bone marrow\u2013derived DCs with OVA and OT-II T cells. In this system, Nrf2\u2212\/\u2212 DCs promoted a Th2\/regulatory T cell response as opposed to a Th1\/Th17 response by WT DCs. This was recapitulated in vivo with superinfected Nrf2\u2212\/\u2212 mice having increased regulatory T cell populations. We also observed an increased median survival time of Nrf2\u2212\/\u2212 superinfected mice, due at least in part to increased IL-10 signaling, as anti\u2013IL-10R Ab treatment reduced median survival time to levels seen in WT mice. Overall, these data suggest that loss of Nrf2 promotes differential T cell skewing mediated by DCs that promote a regulatory phenotype, increasing superinfection survival time, despite increased bacterial burden.<\/jats:p>","DOI":"10.4049\/jimmunol.2400322","type":"journal-article","created":{"date-parts":[[2024,11,1]],"date-time":"2024-11-01T12:41:48Z","timestamp":1730464908000},"page":"1834-1843","source":"Crossref","is-referenced-by-count":6,"title":["Nrf2 Regulates Inflammation by Modulating Dendritic Cell\u2013T Cell Crosstalk during Viral\u2013Bacterial Superinfection"],"prefix":"10.1093","volume":"213","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-1658-3701","authenticated-orcid":false,"given":"Alexis M","family":"Duray","sequence":"first","affiliation":[{"name":"Department of Pediatrics, UPMC Children\u2019s Hospital of Pittsburgh , Pittsburgh, PA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Leigh M","family":"Miller","sequence":"additional","affiliation":[{"name":"Department of Pediatrics, UPMC Children\u2019s Hospital of Pittsburgh , Pittsburgh, PA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9460-3985","authenticated-orcid":false,"given":"Brooke P","family":"Dresden","sequence":"additional","affiliation":[{"name":"Department of Pediatrics, UPMC Children\u2019s Hospital of Pittsburgh , Pittsburgh, PA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0003-1291-060X","authenticated-orcid":false,"given":"Flavia","family":"Rago","sequence":"additional","affiliation":[{"name":"Department of Pediatrics, UPMC Children\u2019s Hospital of Pittsburgh , Pittsburgh, PA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8451-0600","authenticated-orcid":false,"given":"Danielle","family":"Antos","sequence":"additional","affiliation":[{"name":"Department of Pediatrics, UPMC Children\u2019s Hospital of Pittsburgh , Pittsburgh, PA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kevin J","family":"McHugh","sequence":"additional","affiliation":[{"name":"Department of Pediatrics, UPMC Children\u2019s Hospital of Pittsburgh , Pittsburgh, PA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5997-7711","authenticated-orcid":false,"given":"John F","family":"Alcorn","sequence":"additional","affiliation":[{"name":"Department of Pediatrics, UPMC Children\u2019s Hospital of Pittsburgh , Pittsburgh, PA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"286","published-online":{"date-parts":[[2024,11,1]]},"reference":[{"key":"2025020609303919600_r1","doi-asserted-by":"crossref","first-page":"1204","DOI":"10.1016\/S0140-6736(20)30925-9","article-title":"Global burden of 369 diseases and injuries in 204 countries and territories, 1990-2019: a systematic analysis for the Global Burden of Disease Study 2019","volume":"396","author":"Vos","year":"2020","journal-title":"Lancet"},{"key":"2025020609303919600_r2","doi-asserted-by":"crossref","first-page":"1108","DOI":"10.15585\/mmwr.mm7241a2","article-title":"High influenza incidence and disease severity among children and adolescents aged &lt;18 years\u2014United States, 2022\u201323 season","volume":"72","author":"White","year":"2023","journal-title":"MMWR Morb. 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