{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,20]],"date-time":"2026-10-20T14:29:25Z","timestamp":1792506565422,"version":"4.5.0"},"reference-count":33,"publisher":"Oxford University Press (OUP)","issue":"8","license":[{"start":{"date-parts":[[2002,10,1]],"date-time":"2002-10-01T00:00:00Z","timestamp":1033430400000},"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":[[2002,10,15]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>The subversion of microbicidal functions of macrophages by intracellular pathogens is critical for their survival and pathogenicity. The replication of Coxiella burnetii, the agent of Q fever, in acidic phagolysosomes of nonphagocytic cells has been considered as a paradigm of intracellular life of bacteria. We show in this study that C. burnetii survival in THP-1 monocytes was not related to phagosomal pH because bacterial vacuoles were acidic independently of C. burnetii virulence. In contrast, virulent C. burnetii escapes killing in resting THP-1 cells by preventing phagosome maturation. Indeed, C. burnetii vacuoles did not fuse with lysosomes because they were devoid of cathepsin D, and did not accumulate lysosomal trackers; the acquisition of markers of late endosomes and late endosomes-early lysosomes was conserved. In contrast, avirulent variants of C. burnetii were eliminated by monocytes and their vacuoles accumulated late endosomal and lysosomal markers. The fate of virulent C. burnetii in THP-1 monocytes depends on cell activation. Monocyte activation by IFN-\u03b3 restored C. burnetii killing and phagosome maturation as assessed by colocalization of C. burnetii with active cathepsin D. In addition, when IFN-\u03b3 was added before cell infection, it was able to stimulate C. burnetii killing but it also induced vacuolar alkalinization. These findings suggest that IFN-\u03b3 mediates C. burnetii killing via two distinct mechanisms, phagosome maturation, and phagosome alkalinization. Thus, the tuning of vacuole biogenesis is likely a key part of C. burnetii survival and the pathophysiology of Q fever.<\/jats:p>","DOI":"10.4049\/jimmunol.169.8.4488","type":"journal-article","created":{"date-parts":[[2014,4,20]],"date-time":"2014-04-20T20:03:53Z","timestamp":1398024233000},"page":"4488-4495","source":"Crossref","is-referenced-by-count":132,"title":["<i>Coxiella<\/i>\n                    \u00a0\n                    <i>burnetii<\/i>\n                    Survival in THP-1 Monocytes Involves the Impairment of Phagosome Maturation: IFN-\u03b3 Mediates its Restoration and Bacterial Killing"],"prefix":"10.1093","volume":"169","author":[{"given":"Eric","family":"Ghigo","sequence":"first","affiliation":[{"name":"Unite\u0301 des Rickettsies, Faculte\u0301 de Me\u0301decine, Centre National de la Recherche Scientifique Unite\u0301 Mixte de Recherche 6020 , Marseille ,","place":["France"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Christian","family":"Capo","sequence":"additional","affiliation":[{"name":"Unite\u0301 des Rickettsies, Faculte\u0301 de Me\u0301decine, Centre National de la Recherche Scientifique Unite\u0301 Mixte de Recherche 6020 , Marseille ,","place":["France"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ching-Hsuan","family":"Tung","sequence":"additional","affiliation":[{"name":"Center for Molecular Imaging Research, Massachusetts General Hospital, Harvard Medical School , Charlestown, MA 02129"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Didier","family":"Raoult","sequence":"additional","affiliation":[{"name":"Unite\u0301 des Rickettsies, Faculte\u0301 de Me\u0301decine, Centre National de la Recherche Scientifique Unite\u0301 Mixte de Recherche 6020 , Marseille ,","place":["France"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jean-Pierre","family":"Gorvel","sequence":"additional","affiliation":[{"name":"Centre d\u2019Immunologie de Marseille-Luminy , Marseille ,","place":["France"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jean-Louis","family":"Mege","sequence":"additional","affiliation":[{"name":"Unite\u0301 des Rickettsies, Faculte\u0301 de Me\u0301decine, Centre National de la Recherche Scientifique Unite\u0301 Mixte de Recherche 6020 , Marseille ,","place":["France"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"286","published-online":{"date-parts":[[2002,10,15]]},"reference":[{"key":"2026020210024203000_R1","first-page":"518","volume-title":"Clin. 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