{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,6]],"date-time":"2026-10-06T21:42:20Z","timestamp":1791322940796,"version":"4.3.1"},"reference-count":79,"publisher":"Rockefeller University Press","issue":"2","content-domain":{"domain":["rupress.org"],"crossmark-restriction":true},"short-container-title":[],"published-print":{"date-parts":[[2006,2,20]]},"abstract":"<jats:p>The live attenuated yellow fever vaccine 17D (YF-17D) is one of the most effective vaccines available, with a 65-yr history of use in &amp;gt;400 million people globally. Despite this efficacy, there is presently no information about the immunological mechanisms by which YF-17D acts. Here, we present data that suggest that YF-17D activates multiple Toll-like receptors (TLRs) on dendritic cells (DCs) to elicit a broad spectrum of innate and adaptive immune responses. Specifically, YF-17D activates multiple DC subsets via TLRs 2, 7, 8, and 9 to elicit the proinflammatory cytokines interleukin (IL)-12p40, IL-6, and interferon-\u03b1. Interestingly, the resulting adaptive immune responses are characterized by a mixed T helper cell (Th)1\/Th2 cytokine profile and antigen-specific CD8+ T cells. Furthermore, distinct TLRs appear to differentially control the Th1\/Th2 balance; thus, whilst MyD88-deficient mice show a profound impairment of Th1 cytokines, TLR2-deficient mice show greatly enhanced Th1 and Tc1 responses to YF-17D. Together, these data enhance our understanding of the molecular mechanism of action of YF-17D, and highlight the potential of vaccination strategies that use combinations of different TLR ligands to stimulate polyvalent immune responses.<\/jats:p>","DOI":"10.1084\/jem.20051720","type":"journal-article","created":{"date-parts":[[2006,2,6]],"date-time":"2006-02-06T20:23:49Z","timestamp":1139257429000},"page":"413-424","update-policy":"https:\/\/doi.org\/10.1084\/jem.crossmarkpolicy","source":"Crossref","is-referenced-by-count":498,"title":["Yellow fever vaccine YF-17D activates multiple dendritic cell subsets via TLR2, 7, 8, and 9 to stimulate polyvalent immunity"],"prefix":"10.1084","volume":"203","author":[{"given":"Troy","family":"Querec","sequence":"first","affiliation":[{"name":"1Emory Vaccine Center"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Soumaya","family":"Bennouna","sequence":"additional","affiliation":[{"name":"1Emory Vaccine Center"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sefik","family":"Alkan","sequence":"additional","affiliation":[{"name":"33M Pharmaceuticals, St. Paul, MN 55144"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yasmina","family":"Laouar","sequence":"additional","affiliation":[{"name":"4Section of Immunobiology, Yale University School of Medicine, New Haven, CT 06520"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Keith","family":"Gorden","sequence":"additional","affiliation":[{"name":"33M Pharmaceuticals, St. Paul, MN 55144"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Richard","family":"Flavell","sequence":"additional","affiliation":[{"name":"4Section of Immunobiology, Yale University School of Medicine, New Haven, CT 06520"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shizuo","family":"Akira","sequence":"additional","affiliation":[{"name":"5Department of Host Defense, Research Institute for Microbial Diseases, Osaka University, Suita, Osaka 565-0871, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rafi","family":"Ahmed","sequence":"additional","affiliation":[{"name":"1Emory Vaccine Center"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Bali","family":"Pulendran","sequence":"additional","affiliation":[{"name":"1Emory Vaccine Center"},{"name":"2Department of Pathology, Emory University, Atlanta, GA 30329"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"291","published-online":{"date-parts":[[2006,2,6]]},"reference":[{"key":"2023072513442927300_BIB1","doi-asserted-by":"crossref","first-page":"787","DOI":"10.1084\/jem.65.6.787","volume":"65","year":"1937","journal-title":"J. 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