Department of Veterinary Biosciences, College of Veterinary Medicine, The Ohio State University, Columbus, OH 43210, USA.
Clin Microbiol Rev. 2011 Jul;24(3):469-89. doi: 10.1128/CMR.00064-10.
Anaplasma phagocytophilum persists in nature by cycling between mammals and ticks. Human infection by the bite of an infected tick leads to a potentially fatal emerging disease called human granulocytic anaplasmosis. A. phagocytophilum is an obligatory intracellular bacterium that replicates inside mammalian granulocytes and the salivary gland and midgut cells of ticks. A. phagocytophilum evolved the remarkable ability to hijack the regulatory system of host cells. A. phagocytophilum alters vesicular traffic to create an intracellular membrane-bound compartment that allows replication in seclusion from lysosomes. The bacterium downregulates or actively inhibits a number of innate immune responses of mammalian host cells, and it upregulates cellular cholesterol uptake to acquire cholesterol for survival. It also upregulates several genes critical for the infection of ticks, and it prolongs tick survival at freezing temperatures. Several host factors that exacerbate infection have been identified, including interleukin-8 (IL-8) and cholesterol. Host factors that overcome infection include IL-12 and gamma interferon (IFN-γ). Two bacterial type IV secretion effectors and several bacterial proteins that associate with inclusion membranes have been identified. An understanding of the molecular mechanisms underlying A. phagocytophilum infection will foster the development of creative ideas to prevent or treat this emerging tick-borne disease.
嗜吞噬细胞无形体在自然界中通过在哺乳动物和蜱之间循环来生存。人类被感染的蜱叮咬会导致一种潜在致命的新发疾病，称为人粒细胞无形体病。嗜吞噬细胞无形体是一种必需的细胞内细菌，它在哺乳动物的粒细胞和蜱的唾液腺和中肠细胞内复制。嗜吞噬细胞无形体进化出了一种非凡的能力，可以劫持宿主细胞的调节系统。嗜吞噬细胞无形体改变了小泡运输，从而创造了一个细胞内的膜结合隔室，允许在与溶酶体隔离的情况下进行复制。该细菌下调或主动抑制哺乳动物宿主细胞的许多固有免疫反应，并上调细胞胆固醇摄取以获取生存所需的胆固醇。它还上调了几个对蜱感染至关重要的基因，并延长了蜱在冷冻温度下的存活时间。已经确定了一些加剧感染的宿主因素，包括白细胞介素-8（IL-8）和胆固醇。克服感染的宿主因素包括白细胞介素-12 和γ干扰素（IFN-γ）。已经鉴定出两种细菌 IV 型分泌效应子和几种与包含膜相关的细菌蛋白。对嗜吞噬细胞无形体感染的分子机制的理解将促进创造性思维的发展，以预防或治疗这种新出现的蜱传疾病。
