Carlyon Jason A, Fikrig Erol
Department of Microbiology, Immunology, and Molecular Genetics, University of Kentucky College of Medicine, Lexington, Kentucky 40536-0298, USA.
Curr Opin Hematol. 2006 Jan;13(1):28-33. doi: 10.1097/01.moh.0000190109.00532.56.
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.
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.
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.
本综述总结了关于嗜吞噬细胞无形体用于逃避或颠覆中性粒细胞杀伤机制以及改变其他中性粒细胞途径以促进其存活的策略的最新知识。
嗜吞噬细胞无形体通过阻止携带细胞色素b558的特异性颗粒和分泌小泡与细胞质区室膜融合来逃避中性粒细胞的氧化杀伤。它还能直接使超氧阴离子解毒。此外，该细菌改变转录因子与CYYB启动子的相互作用，导致gp91phox水平大幅降低，进而使呼吸爆发能力下降。嗜吞噬细胞无形体不仅不能激活因细菌摄取而刺激的正常中性粒细胞凋亡分化程序，还通过操纵促凋亡和抗凋亡基因的表达来延迟自发凋亡。促凋亡因子Bfl-1的维持至少部分有助于维持线粒体膜完整性并抑制半胱天冬酶3的激活。
嗜吞噬细胞无形体通过清除O2、抑制其液泡膜上NADPH氧化酶的组装以及改变关键NADPH氧化酶成分gp91phox的启动子活性来对抗中性粒细胞的氧化杀伤。摄取这种独特的病原体不会诱导中性粒细胞凋亡。此外，嗜吞噬细胞无形体通过失调中性粒细胞基因表达和分子机制来延长其原本寿命短暂的宿主细胞的寿命，从而可能最大限度地提高其在哺乳动物宿主体内的存活和传播能力。
