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In all cell types examined,<jats:italic>C. burnetii<\/jats:italic>establishes a replicative niche in a lysosome-like parasitophorous vacuole where it carries out a lengthy infectious cycle with minimal cytopathic effects. The persistent and mild nature of<jats:italic>C. burnetii<\/jats:italic>infection in vitro suggests that the pathogen modulates apoptosis to sustain the host cell. In the current study, we examined the ability of<jats:italic>C. burnetii<\/jats:italic>to inhibit apoptotic cell death during infection of human THP-1 monocyte-derived macrophages and primary monkey alveolar macrophages.<jats:italic>C. burnetii<\/jats:italic>-infected cells demonstrated significant protection from death relative to uninfected cells following treatment with staurosporine, a potent inducer of intrinsic apoptosis. This protection correlated with reduced cleavage of caspase-9, caspase-3, and poly(ADP-ribose) polymerase (PARP), all proteolytic events that occur during apoptosis. Reduced PARP cleavage was also observed in cells treated with tumor necrosis factor alpha to induce extrinsic apoptosis. Apoptosis inhibition was a<jats:italic>C. burnetii<\/jats:italic>-driven process as infected cells treated with rifampin or chloramphenicol, inhibitors of bacterial RNA and protein synthesis, respectively, showed significantly reduced protection against staurosporine-induced apoptosis.<jats:italic>C. burnetii<\/jats:italic>infection affected the expression of multiple apoptosis-related genes and resulted in increased synthesis of the antiapoptotic proteins A1\/Bfl-1 and c-IAP2. Collectively, these data suggest that<jats:italic>C. burnetii<\/jats:italic>modulates apoptotic pathways to inhibit host cell death, thus providing a stable, intracellular niche for the course of the pathogen's infectious cycle.<\/jats:p>","DOI":"10.1128\/iai.00594-07","type":"journal-article","created":{"date-parts":[[2007,7,3]],"date-time":"2007-07-03T00:34:01Z","timestamp":1183422841000},"page":"4263-4271","update-policy":"https:\/\/doi.org\/10.1128\/asmj-crossmark-policy-page","source":"Crossref","is-referenced-by-count":124,"title":["<i>Coxiella burnetii<\/i>Inhibits Apoptosis in Human THP-1 Cells and Monkey Primary Alveolar Macrophages"],"prefix":"10.1128","volume":"75","author":[{"given":"Daniel E.","family":"Voth","sequence":"first","affiliation":[{"name":"Coxiella Pathogenesis Section, Laboratory of Intracellular Parasites, Rocky Mountain Laboratories, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Hamilton, Montana 59840"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dale","family":"Howe","sequence":"additional","affiliation":[{"name":"Coxiella Pathogenesis Section, Laboratory of Intracellular Parasites, Rocky Mountain Laboratories, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Hamilton, Montana 59840"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Robert A.","family":"Heinzen","sequence":"additional","affiliation":[{"name":"Coxiella Pathogenesis Section, Laboratory of Intracellular Parasites, Rocky Mountain Laboratories, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Hamilton, Montana 59840"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"235","reference":[{"key":"e_1_3_2_2_2","first-page":"246","volume":"9","year":"2006","unstructured":"Abu-Zant, A., S. 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