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Infection and Immunity, September 2007, p. 4263-4271, Vol. 75, No. 9
0019-9567/07/$08.00+0     doi:10.1128/IAI.00594-07
Copyright © 2007, American Society for Microbiology. All Rights Reserved.

Coxiella burnetii Inhibits Apoptosis in Human THP-1 Cells and Monkey Primary Alveolar Macrophages

Coxiella Pathogenesis Section, Laboratory of Intracellular Parasites, Rocky Mountain Laboratories, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Hamilton, Montana 59840

Received 25 April 2007/ Returned for modification 29 May 2007/ Accepted 15 June 2007

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.

Published ahead of print on 2 July 2007.

Editor: F. C. Fang

This article has been cited by other articles:

• Luhrmann, A., Roy, C. R. (2007). Coxiella burnetii Inhibits Activation of Host Cell Apoptosis through a Mechanism That Involves Preventing Cytochrome c Release from Mitochondria. Infect. Immun. 75: 5282-5289 [Abstract] [Full Text]