Anaplasma phagocytophilum Manipulates Host Cell Apoptosis by Different Mechanisms to Establish Infection.
Anaplasma phagocytophilum Manipulates Host Cell Apoptosis by Different Mechanisms to Establish Infection.
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DOI：
10.3390/vetsci3030015
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发表时间：
2016-07-15
影响因子：
2.4
通讯作者：
de la Fuente J
中科院分区：
文献类型：
--
作者：
Alberdi P;Espinosa PJ;Cabezas-Cruz A;de la Fuente J
嗜吞噬细胞无形体是一种引起人和动物粒细胞无形体病和反刍动物蜱传热的人畜共患病原体。这种专性细胞内细菌进化为使用共同策略在脊椎动物宿主和蜱媒介中建立感染。在此，我们讨论了病原体用于调节细胞凋亡和建立宿主细胞感染的不同策略。在脊椎动物中性粒细胞和人早幼粒细胞HL-60中，促凋亡因子和抗凋亡因子均已被报道。蜱对感染反应的组织特异性差异和细胞凋亡途径的差异调节已在成年雌性中肠和唾液腺中观察到。嗜吞噬细胞菌在蜱中肠，病原体通过Janus激酶/信号转导和转录激活因子（JAK/STAT）途径抑制细胞凋亡，而在唾液腺，内源性凋亡途径被抑制，但蜱细胞通过激活外源性凋亡途径应答。在肩突硬蜱ISE 6细胞中，细菌感染下调线粒体孔蛋白并操纵内质网中的蛋白质加工和细胞葡萄糖代谢以抑制细胞凋亡并促进感染，而在IRE/CTVM 20蜱细胞中，细胞凋亡的抑制似乎由较低的半胱天冬酶水平调节。这些结果表明A.嗜吞噬细胞菌使用不同的机制来抑制脊椎动物和无脊椎动物宿主感染的细胞凋亡。
Anaplasma phagocytophilum is an emerging zoonotic pathogen that causes human and animal granulocytic anaplasmosis and tick-borne fever of ruminants. This obligate intracellular bacterium evolved to use common strategies to establish infection in both vertebrate hosts and tick vectors. Herein, we discuss the different strategies used by the pathogen to modulate cell apoptosis and establish infection in host cells. In vertebrate neutrophils and human promyelocytic cells HL-60, both pro-apoptotic and anti-apoptotic factors have been reported. Tissue-specific differences in tick response to infection and differential regulation of apoptosis pathways have been observed in adult female midguts and salivary glands in response to infection with A. phagocytophilum. In tick midguts, pathogen inhibits apoptosis through the Janus kinase/signal transducers and activators of transcription (JAK/STAT) pathway, while in salivary glands, the intrinsic apoptosis pathways is inhibited but tick cells respond with the activation of the extrinsic apoptosis pathway. In Ixodes scapularis ISE6 cells, bacterial infection down-regulates mitochondrial porin and manipulates protein processing in the endoplasmic reticulum and cell glucose metabolism to inhibit apoptosis and facilitate infection, whereas in IRE/CTVM20 tick cells, inhibition of apoptosis appears to be regulated by lower caspase levels. These results suggest that A. phagocytophilum uses different mechanisms to inhibit apoptosis for infection of both vertebrate and invertebrate hosts.