title: Early induction and late abrogation of respiratory burst in A. phagocytophilum-infected neutrophils.
abstract: Human granulocytic ehrlichiosis is an emerging tick-borne disease caused by the obligate intracellular pathogen, Anaplasma phagocytophilum. This organism is unique because it survives and propagates in neutrophil vacuoles. During phagocytosis professional phagocytes increase oxygen consumption (respiratory burst) through the activity of NADPH-oxidase, which generates superoxide anion (O2(-)) and hydrogen peroxide (H(2)O(2)). We assayed the ability of A. phagocytophilum-infected neutrophils to generate O2(-) in response to early infection (0, 3, and 5 hours) by using 2',7'-dichlorodihydrofluorescein diacetate (DCFH-DA), a fluorogenic probe commonly used to detect cellular production of reactive oxygen species (ROS). Our flow cytometric analyses showed that cell-free A. phagocytophilum induced respiratory burst 6.9-fold greater than that of LPS, an effect still evident to a lesser degree after 3 h, but absent by 5h. A. phagocytophilum initially induces and then represses respiratory burst in neutrophils. The long-term reduction in respiratory burst activity may be important for survival of A. phagocytophilum and other infectious agents in neutrophils. The effect of this may be to generate a limited functional equivalent of chronic granulomatous disease that predisposes to infections by opportunistic pathogens.
authors.affiliation: Division of Medical Microbiology, Department of Pathology, The Johns Hopkins University School of Medicine, Baltimore, Maryland 21205, USA. kchoi3@jhmi.edu
authors.forename: Kyoung-Seong
authors.initials: KS
authors.lastname: Choi
authors.forename: J Stephen
authors.initials: JS
authors.lastname: Dumler
mesh_terms: D041081:Anaplasma phagocytophilum / Q000254:growth & development / Q000502:physiology*; D002474:Cell-Free System; D006801:Humans; D066298:In Vitro Techniques; D008070:Lipopolysaccharides / Q000494:pharmacology; D009504:Neutrophils / Q000187:drug effects / Q000382:microbiology* / Q000502:physiology*; D016897:Respiratory Burst / Q000502:physiology*
chemical_list: D008070:Lipopolysaccharides