Mechanisms of evasion of neutrophil killing by Anaplasma phagocytophilum

作者：Carlyon JA^*; Fikrig E

来源：Current Opinion in Hematology, 2006, 13(1): 28-33.

DOI：10.1097/01.moh.0000190109.00532.56

• apoptosis
• human granulocytic anaplasmosis
• human granulocytic ehrlichiosis
• intracellular pathogen
• oxidative killing

Purpose of review. 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.
Recent findings. A. phagocytophilum evades neutrophil oxidative killing by preventing fusion of cytochrome b(558)-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 gp91(phox) 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.
Summary. A. phagocytophilum combats neutrophil oxidative killing by scavenging O-2(-), inhibiting NADPH oxidase assembly on its vacuolar membrane, and modifying promoter activity for a key NADPH oxidase component, gp91(phox). 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.

• 出版日期2006-1