| Coxiella burnetii inhibits apoptosis in human THP-1 cells and monkey primary alveolar macrophages. | |
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MedLine Citation:
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PMID: 17606599 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
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Coxiella burnetii, the cause of human Q fever, is an aerosol-borne, obligate intracellular bacterium that targets host alveolar mononuclear phagocytic cells during infection. In all cell types examined, C. burnetii 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 C. burnetii infection in vitro suggests that the pathogen modulates apoptosis to sustain the host cell. In the current study, we examined the ability of C. burnetii to inhibit apoptotic cell death during infection of human THP-1 monocyte-derived macrophages and primary monkey alveolar macrophages. C. burnetii-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 C. burnetii-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. C. burnetii 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 C. burnetii modulates apoptotic pathways to inhibit host cell death, thus providing a stable, intracellular niche for the course of the pathogen's infectious cycle. |
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Authors:
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Daniel E Voth; Dale Howe; Robert A Heinzen |
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Publication Detail:
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Type: Journal Article; Research Support, Non-U.S. Gov't Date: 2007-07-02 |
Journal Detail:
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Title: Infection and immunity Volume: 75 ISSN: 0019-9567 ISO Abbreviation: Infect. Immun. Publication Date: 2007 Sep |
Date Detail:
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Created Date: 2007-08-20 Completed Date: 2007-10-10 Revised Date: 2009-11-18 |
Medline Journal Info:
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Nlm Unique ID: 0246127 Medline TA: Infect Immun Country: United States |
Other Details:
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Languages: eng Pagination: 4263-71 Citation Subset: IM |
Affiliation:
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Laboratory of Intracellular Parasites, Rocky Mountain Laboratories, 903 S. 4th Street, Hamilton, MT 59840, USA. |
Export Citation:
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APA/MLA Format Download EndNote Download BibTex |
| MeSH Terms | |
Descriptor/Qualifier:
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Animals Apoptosis / drug effects, physiology* Caspases / antagonists & inhibitors, metabolism Cell Line, Tumor Cercopithecus aethiops Coxiella burnetii / physiology* Humans Macrophages, Alveolar / cytology*, enzymology, microbiology* Monocytes / cytology, drug effects, enzymology, microbiology Staurosporine / pharmacology Vero Cells |
| Chemical | |
Reg. No./Substance:
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62996-74-1/Staurosporine; EC 3.4.22.-/Caspases |
| Comments/Corrections | |
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
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