期刊
MICROBES AND INFECTION
卷 11, 期 6-7, 页码 671-679出版社
ELSEVIER SCIENCE BV
DOI: 10.1016/j.micinf.2009.04.005
关键词
Neutrophil; NADPH oxidase; Coxiella; Phagocytosis; Superoxide anion
资金
- National Institutes of Health [P20 RR-020185, U54 Al-065357]
- M.J. Murdock Charitable Trust
- Montana State University Agricultural Experimental Station
Coxiella burnetii is an obligate intracellular Gram-negative pathogen. A notable feature of C. burnetii is its ability to replicate within acidic phagolysosomes; however, the mechanisms utilized in evading host defenses are not well defined. Here, we investigated human neutrophil phagocytosis of C. burnetii (Nine Mile, phase II; NMII) and the effect of phagocytosed organisms on neutrophil reactive oxygen species (ROS) production. We found that opsonization with immune serum substantially enhanced phagocytosis of NMII Human neutrophils phagocytosing opsonized NMII generated very little ROS compared to cells phagocytosing opsonized Staphylococcus aureus, Escherichia coli, or zymosan. However, phagocytosis of NMII did not affect the subsequent ROS response to a soluble agonist, indicating inhibition was localized to the phagolysosome and was not a global effect. Indeed, analysis of NADPH oxidase assembly in neutrophils after phagocytosis showed that translocation of cytosolic NADPH oxidase proteins, p47(phox) and p67(phox), to the membrane was absent in cells phagocytosing NMII, as compared to cells phagocytosing S. aureus or activated by phorbol myristate acetate. Thus, phagocytosed NMII is able to disrupt assembly of the human neutrophil NADPH oxidase, which represents a novel virulence mechanism for this organism and appears to be a common mechanism of virulence for many intracellular pathogens. (C) 2009 Elsevier Masson SAS. All rights reserved.
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