{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,9]],"date-time":"2026-10-09T19:21:13Z","timestamp":1791573673366,"version":"4.3.4"},"reference-count":44,"publisher":"Oxford University Press (OUP)","issue":"6","license":[{"start":{"date-parts":[[2004,3,1]],"date-time":"2004-03-01T00:00:00Z","timestamp":1078099200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/academic.oup.com\/pages\/standard-publication-reuse-rights"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2004,3,15]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>The role of Toll-like receptors (TLRs) in the recognition of extracellular and facultative intracellular bacteria by the innate immune system has been extensively studied, but their role in the recognition of obligate intracellular organisms remains unknown. Coxiella burnetii, the agent of Q fever, is an obligate intracellular bacterium that specifically inhabits monocytes\/macrophages. We showed in this study that C. burnetii LPS is involved in the uptake of virulent organisms by macrophages but not in that of avirulent variants. The uptake of virulent organisms was dependent on TLR4 because it was reduced in macrophages from TLR4\u2212\/\u2212 mice. In addition, LPS was responsible for filamentous actin reorganization induced by virulent C. burnetii, which was prevented in TLR4\u2212\/\u2212 macrophages. In contrast, the intracellular fate of C. burnetii was not affected in TLR4\u2212\/\u2212 macrophages, suggesting that TLR4 does not control the maturation of C. burnetii phagosome and the microbicidal activity of macrophages. These results are consistent with in vivo experiments because the pattern of tissue infection and the clearance of C. burnetii were similar in wild-type and TLR4\u2212\/\u2212 mice. We also showed that the number of granulomas was decreased in the liver of infected TLR4\u2212\/\u2212 mice, and the formation of splenic granulomas was only transient. The impaired formation of granulomas was associated with decreased production of IFN-\u03b3 and TNF. Taken together, these results demonstrate that TLR4 controls early events of C. burnetii infection such as macrophage phagocytosis, granuloma formation, and cytokine production.<\/jats:p>","DOI":"10.4049\/jimmunol.172.6.3695","type":"journal-article","created":{"date-parts":[[2014,4,20]],"date-time":"2014-04-20T21:59:29Z","timestamp":1398031169000},"page":"3695-3703","source":"Crossref","is-referenced-by-count":108,"title":["Lipopolysaccharide from\n                    <i>Coxiella burnetii<\/i>\n                    Is Involved in Bacterial Phagocytosis, Filamentous Actin Reorganization, and Inflammatory Responses through Toll-Like Receptor 4"],"prefix":"10.1093","volume":"172","author":[{"given":"Ame\u0301lie","family":"Honstettre","sequence":"first","affiliation":[{"name":"Unite\u0301 des Rickettsies, Centre National de la Recherche Scientifique Unite\u0301 Mixte de Recherche 6020, Institut Federatif de Recherche 48 Universite\u0301 de la Me\u0301diterrane\u0301e , Marseille ,","place":["France"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Eric","family":"Ghigo","sequence":"additional","affiliation":[{"name":"Unite\u0301 des Rickettsies, Centre National de la Recherche Scientifique Unite\u0301 Mixte de Recherche 6020, Institut Federatif de Recherche 48 Universite\u0301 de la Me\u0301diterrane\u0301e , Marseille ,","place":["France"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alix","family":"Moynault","sequence":"additional","affiliation":[{"name":"Unite\u0301 des Rickettsies, Centre National de la Recherche Scientifique Unite\u0301 Mixte de Recherche 6020, Institut Federatif de Recherche 48 Universite\u0301 de la Me\u0301diterrane\u0301e , Marseille ,","place":["France"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Christian","family":"Capo","sequence":"additional","affiliation":[{"name":"Unite\u0301 des Rickettsies, Centre National de la Recherche Scientifique Unite\u0301 Mixte de Recherche 6020, Institut Federatif de Recherche 48 Universite\u0301 de la Me\u0301diterrane\u0301e , Marseille ,","place":["France"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rudolf","family":"Toman","sequence":"additional","affiliation":[{"name":"Department of Rickettsiology and Chlamydiology, Institute of Virology, Slovak Academy of Sciences , Bratislava ,","place":["Slovak Republik"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shizuo","family":"Akira","sequence":"additional","affiliation":[{"name":"Department of Host Defense, Research Institute for Microbial Diseases, Osaka University , Osaka ,","place":["Japan"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Osamu","family":"Takeuchi","sequence":"additional","affiliation":[{"name":"Department of Host Defense, Research Institute for Microbial Diseases, Osaka University , Osaka ,","place":["Japan"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hubert","family":"Lepidi","sequence":"additional","affiliation":[{"name":"Unite\u0301 des Rickettsies, Centre National de la Recherche Scientifique Unite\u0301 Mixte de Recherche 6020, Institut Federatif de Recherche 48 Universite\u0301 de la Me\u0301diterrane\u0301e , Marseille ,","place":["France"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Didier","family":"Raoult","sequence":"additional","affiliation":[{"name":"Unite\u0301 des Rickettsies, Centre National de la Recherche Scientifique Unite\u0301 Mixte de Recherche 6020, Institut Federatif de Recherche 48 Universite\u0301 de la Me\u0301diterrane\u0301e , Marseille ,","place":["France"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jean-Louis","family":"Mege","sequence":"additional","affiliation":[{"name":"Unite\u0301 des Rickettsies, Centre National de la Recherche Scientifique Unite\u0301 Mixte de Recherche 6020, Institut Federatif de Recherche 48 Universite\u0301 de la Me\u0301diterrane\u0301e , Marseille ,","place":["France"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"286","published-online":{"date-parts":[[2004,3,15]]},"reference":[{"key":"2026020211210674600_R1","first-page":"298","volume-title":"Science","year":"2002"},{"key":"2026020211210674600_R2","first-page":"135","volume-title":"Nat. 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