{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,15]],"date-time":"2026-07-15T22:48:28Z","timestamp":1784155708548,"version":"3.55.0"},"reference-count":42,"publisher":"MDPI AG","issue":"6","license":[{"start":{"date-parts":[[2023,6,12]],"date-time":"2023-06-12T00:00:00Z","timestamp":1686528000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"NIH","award":["R21AI133215"],"award-info":[{"award-number":["R21AI133215"]}]},{"name":"NIH","award":["R01 AI1134733"],"award-info":[{"award-number":["R01 AI1134733"]}]},{"name":"NIH","award":["AI125446"],"award-info":[{"award-number":["AI125446"]}]},{"name":"NIH","award":["AI127481"],"award-info":[{"award-number":["AI127481"]}]},{"name":"NIH","award":["AI167058"],"award-info":[{"award-number":["AI167058"]}]},{"name":"NIH","award":["IK6 BX005392"],"award-info":[{"award-number":["IK6 BX005392"]}]},{"name":"VA Senior Research Career Scientist Award","award":["R21AI133215"],"award-info":[{"award-number":["R21AI133215"]}]},{"name":"VA Senior Research Career Scientist Award","award":["R01 AI1134733"],"award-info":[{"award-number":["R01 AI1134733"]}]},{"name":"VA Senior Research Career Scientist Award","award":["AI125446"],"award-info":[{"award-number":["AI125446"]}]},{"name":"VA Senior Research Career Scientist Award","award":["AI127481"],"award-info":[{"award-number":["AI127481"]}]},{"name":"VA Senior Research Career Scientist Award","award":["AI167058"],"award-info":[{"award-number":["AI167058"]}]},{"name":"VA Senior Research Career Scientist Award","award":["IK6 BX005392"],"award-info":[{"award-number":["IK6 BX005392"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Viruses"],"abstract":"<jats:p>Macrophages are critical in the pathogenesis of a diverse group of viral pathogens, both as targets of infection and for eliciting primary defense mechanisms. Our prior in vitro work identified that CD40 signaling in murine peritoneal macrophages protects against several RNA viruses by eliciting IL-12, which stimulates the production of interferon gamma (IFN-\u03b3). Here, we examine the role of CD40 signaling in vivo. We show that CD40 signaling is a critical, but currently poorly appreciated, component of the innate immune response using two distinct infectious agents: mouse-adapted influenza A virus (IAV, PR8) and recombinant VSV encoding the Ebola virus glycoprotein (rVSV-EBOV GP). We find that stimulation of CD40 signaling decreases early IAV titers, whereas loss of CD40 elevated early titers and compromised lung function by day 3 of infection. Protection conferred by CD40 signaling against IAV is dependent on IFN-\u03b3 production, consistent with our in vitro studies. Using rVSV-EBOV GP that serves as a low-biocontainment model of filovirus infection, we demonstrate that macrophages are a CD40-expressing population critical for protection within the peritoneum and T-cells are the key source of CD40L (CD154). These experiments reveal the in vivo mechanisms by which CD40 signaling in macrophages regulates the early host responses to RNA virus infection and highlight how CD40 agonists currently under investigation for clinical use may function as a novel class of broad antiviral treatments.<\/jats:p>","DOI":"10.3390\/v15061353","type":"journal-article","created":{"date-parts":[[2023,6,12]],"date-time":"2023-06-12T01:28:21Z","timestamp":1686533301000},"page":"1353","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":5,"title":["CD40 Signaling in Mice Elicits a Broad Antiviral Response Early during Acute Infection with RNA Viruses"],"prefix":"10.3390","volume":"15","author":[{"given":"Kai J.","family":"Rogers","sequence":"first","affiliation":[{"name":"Department of Microbiology and Immunology, University of Iowa, Iowa City, IA 52242, USA"},{"name":"Department of Pathology, University of Iowa, Iowa City, IA 52242, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9488-3101","authenticated-orcid":false,"given":"Paige T.","family":"Richards","sequence":"additional","affiliation":[{"name":"Department of Microbiology and Immunology, University of Iowa, Iowa City, IA 52242, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9157-3469","authenticated-orcid":false,"given":"Zeb R.","family":"Zacharias","sequence":"additional","affiliation":[{"name":"Department of Pathology, University of Iowa, Iowa City, IA 52242, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Laura L.","family":"Stunz","sequence":"additional","affiliation":[{"name":"Department of Microbiology and Immunology, University of Iowa, Iowa City, IA 52242, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rahul","family":"Vijay","sequence":"additional","affiliation":[{"name":"Department of Microbiology and Immunology, University of Iowa, Iowa City, IA 52242, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Noah S.","family":"Butler","sequence":"additional","affiliation":[{"name":"Department of Microbiology and Immunology, University of Iowa, Iowa City, IA 52242, USA"},{"name":"Interdisciplinary Graduate Program in Immunology, University of Iowa, Iowa City, IA 52242, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9800-6854","authenticated-orcid":false,"given":"Kevin L.","family":"Legge","sequence":"additional","affiliation":[{"name":"Department of Microbiology and Immunology, University of Iowa, Iowa City, IA 52242, USA"},{"name":"Department of Pathology, University of Iowa, Iowa City, IA 52242, USA"},{"name":"Interdisciplinary Graduate Program in Immunology, University of Iowa, Iowa City, IA 52242, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1291-5078","authenticated-orcid":false,"given":"Gail A.","family":"Bishop","sequence":"additional","affiliation":[{"name":"Department of Microbiology and Immunology, University of Iowa, Iowa City, IA 52242, USA"},{"name":"Interdisciplinary Graduate Program in Immunology, University of Iowa, Iowa City, IA 52242, USA"},{"name":"Department of Internal Medicine, University of Iowa, Iowa City, IA 52242, USA"},{"name":"Iowa City VA Health Care System, Iowa City, IA 52246, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9892-4484","authenticated-orcid":false,"given":"Wendy","family":"Maury","sequence":"additional","affiliation":[{"name":"Department of Microbiology and Immunology, University of Iowa, Iowa City, IA 52242, USA"},{"name":"Interdisciplinary Graduate Program in Immunology, University of Iowa, Iowa City, IA 52242, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2023,6,12]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"152","DOI":"10.1111\/j.1600-065X.2009.00782.x","article-title":"Molecular mechanism and function of CD40\/CD40L engagement in the immune system","volume":"229","author":"Elgueta","year":"2009","journal-title":"Immunol. 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