title: Mechanisms of evasion of neutrophil killing by Anaplasma phagocytophilum.
abstract: OBJECTIVE
  This review summarizes recent knowledge regarding the strategies employed by Anaplasma phagocytophilum to evade or subvert neutrophil killing mechanisms and modify other neutrophil pathways to promote its survival.
  
  
  RESULTS
  A. phagocytophilum evades neutrophil oxidative killing by preventing fusion of cytochrome b558-carrying specific granules and secretory vesicles with the membrane of its cytoplasmic compartment. It also directly detoxifies superoxide anion. Additionally, the bacterium alters the interaction of transcription factors with the CYYB promoter, which results in greatly reduced gp91phox levels and a consequent decline in respiratory burst capability. A. phagocytophilum not only fails to activate the normal neutrophil apoptosis differentiation program stimulated by bacterial uptake, but also delays spontaneous apoptosis by manipulating the expression of pro and antiapoptotic genes. Maintenance of the proapoptotic factor Bfl-1 contributes, at least in part, to the preservation of mitochondrial membrane integrity and inhibition of caspase 3 activation.
  
  
  CONCLUSIONS
  A. phagocytophilum combats neutrophil oxidative killing by scavenging O2, inhibiting NADPH oxidase assembly on its vacuolar membrane, and modifying promoter activity for a key NADPH oxidase component, gp91phox. Uptake of this unique pathogen fails to induce neutrophil apoptosis. Furthermore, A. phagocytophilum extends the life of its otherwise short-lived host cell by dysregulating neutrophil gene expression and molecular machinery to potentially maximize its survival and dissemination within its mammalian host.
authors.affiliation: Department of Microbiology, Immunology, and Molecular Genetics, University of Kentucky College of Medicine, Lexington, Kentucky 40536-0298, USA. jason.carlyon@uky.edu
authors.forename: Jason A
authors.initials: JA
authors.lastname: Carlyon
authors.forename: Erol
authors.initials: E
authors.lastname: Fikrig
mesh_terms: D041081:Anaplasma phagocytophilum / Q000378:metabolism / Q000472:pathogenicity*; D017209:Apoptosis; D003573:Cytochrome b Group / Q000378:metabolism; D016873:Ehrlichiosis / Q000378:metabolism* / Q000473:pathology; D006801:Humans; D008562:Membrane Glycoproteins / Q000378:metabolism; D015778:Minor Histocompatibility Antigens; D000074662:NADPH Oxidase 2; D019255:NADPH Oxidases / Q000378:metabolism; D009504:Neutrophils / Q000378:metabolism* / Q000382:microbiology / Q000473:pathology; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000378:metabolism; D015398:Signal Transduction
chemical_list: C096816:BCL2-related protein A1; D003573:Cytochrome b Group; D008562:Membrane Glycoproteins; D015778:Minor Histocompatibility Antigens; D019253:Proto-Oncogene Proteins c-bcl-2; C036888:cytochrome b558; C056558:CYBB protein, human; D000074662:NADPH Oxidase 2; D019255:NADPH Oxidases