{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,29]],"date-time":"2026-09-29T19:27:19Z","timestamp":1790710039031,"version":"4.1.0"},"reference-count":89,"publisher":"Oxford University Press (OUP)","issue":"6","license":[{"start":{"date-parts":[[2008,8,15]],"date-time":"2008-08-15T00:00:00Z","timestamp":1218758400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/academic.oup.com\/pages\/standard-publication-reuse-rights"}],"funder":[{"DOI":"10.13039\/100007197","name":"U.S. Public Health Service","doi-asserted-by":"publisher","award":["AI-56460"],"award-info":[{"award-number":["AI-56460"]}],"id":[{"id":"10.13039\/100007197","id-type":"DOI","asserted-by":"publisher"}]},{"name":"Middle Atlantic Regional Center of Excellence for Biodefense and Emerging Infectious Diseases","award":["U54 AI-57168"],"award-info":[{"award-number":["U54 AI-57168"]}]},{"name":"Middle Atlantic Regional Center of Excellence for Biodefense and Emerging Infectious Diseases","award":["AI-18797"],"award-info":[{"award-number":["AI-18797"]}]},{"DOI":"10.13039\/100000060","name":"National Institute of Allergy and Infectious Diseases","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100000060","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2008,12,1]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>Francisella tularensis is the causative agent of tularemia, a severe, debilitating disease of humans and other mammals. As this microorganism is also classified as a \u201ccategory-A pathogen\u201d and a potential biowarfare agent, there is a need for an effective vaccine. Several antigens of F. tularensis, including the heat shock protein DnaK, have been proposed for use in a potential subunit vaccine. In this study, we characterized the innate immune response of murine bone marrow-derived dendritic cells (DC) to F. tularensis DnaK. Recombinant DnaK was produced using a bacterial expression system and purified using affinity, ion-exchange, and size-exclusion chromatography. DnaK induced the activation of MAPKs and NF-\u03baB in DC and the production of the proinflammatory cytokines IL-6, TNF-\u03b1, and IL-12 p40, as well as low levels of IL-10. DnaK induced phenotypic maturation of DC, as demonstrated by an up-regulation of costimulatory molecules CD40, CD80, and CD86. DnaK stimulated DC through TLR4 and the adapters MyD88 and Toll\/IL-1R domain-containing adaptor-inducing IFN-\u03b2 (TRIF) that mediated differential responses. DnaK induced activation of MAPKs and NF-\u03baB in a MyD88- or TRIF-dependent manner. However, the presence of MyD88- and TRIF-dependent signaling pathways was essential for an optimal, DnaK-induced cytokine response in DC. In contrast, DnaK induced DC maturation in a TRIF-dependent, MyD88-independent manner. These results provide insight about the molecular interactions between an immunodominant antigen of F. tularensis and host immune cells, which is crucial for the rational design and development of a safe and efficacious vaccine against tularemia.<\/jats:p>","DOI":"10.1189\/jlb.0308215","type":"journal-article","created":{"date-parts":[[2008,8,15]],"date-time":"2008-08-15T20:44:21Z","timestamp":1218833061000},"page":"1434-1446","source":"Crossref","is-referenced-by-count":48,"title":["TLR4-mediated activation of dendritic cells by the heat shock protein DnaK from\n                    <i>Francisella tularensis<\/i>"],"prefix":"10.1093","volume":"84","author":[{"given":"Amit R","family":"Ashtekar","sequence":"first","affiliation":[{"name":"Department of Microbiology, University of Alabama at Birmingham , Birmingham, Alabama , USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ping","family":"Zhang","sequence":"additional","affiliation":[{"name":"Department of Pediatric Dentistry, University of Alabama at Birmingham , Birmingham, Alabama , USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jannet","family":"Katz","sequence":"additional","affiliation":[{"name":"Department of Pediatric Dentistry, University of Alabama at Birmingham , Birmingham, Alabama , USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Champion C S","family":"Deivanayagam","sequence":"additional","affiliation":[{"name":"Department of Vision Sciences, University of Alabama at Birmingham , Birmingham, Alabama , USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Prasad","family":"Rallabhandi","sequence":"additional","affiliation":[{"name":"Department of Microbiology and Immunology, University of Maryland School of Medicine , Baltimore, Maryland , USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Stefanie N","family":"Vogel","sequence":"additional","affiliation":[{"name":"Department of Microbiology and Immunology, University of Maryland School of Medicine , Baltimore, Maryland , USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Suzanne M","family":"Michalek","sequence":"additional","affiliation":[{"name":"Department of Microbiology, University of Alabama at Birmingham , Birmingham, Alabama , USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"286","published-online":{"date-parts":[[2008,8,15]]},"reference":[{"key":"2023032712373627000_","doi-asserted-by":"crossref","first-page":"2763","DOI":"10.1001\/jama.285.21.2763","article-title":"Tularemia as a biological weapon. 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