Sinai A P, Payne T M, Carmen J C, Hardi L, Watson S J, Molestina R E
Department of Microbiology, Immunology and Molecular Genetics, University of Kentucky College of Medicine, 800 Rose St, Lexington, KY 40536, USA.
Int J Parasitol. 2004 Mar 9;34(3):381-91. doi: 10.1016/j.ijpara.2003.11.009.
The establishment of a productive infection by an obligate intracellular pathogen is dependent on subversion of cellular defences. Apoptosis, or programmed cell death, is a property of metazoan cells that plays a critical role in inhibiting the proliferation of invasive organisms and viruses thereby protecting uninfected cells and limiting damage to the host organism. Not surprisingly, manipulation of the machinery of apoptosis plays a critical role in the pathogenesis of several intracellular pathogens. Toxoplasma gondii, arguably one of the most successful protozoan pathogens, has evolved several strategies to inhibit both the initiation and propagation of the apoptotic cascade. Recent work from several groups indicates an exquisite level of sophistication in the mechanisms to inhibit apoptosis along its diverse pathways. Much of this ability appears to centre around the manipulation of host transcription, specifically of genes involved in the pro-survival/anti-apoptotic response effectively manipulating the infected cell into a highly anti-apoptotic state. The implications of these observations extend beyond Toxoplasma biology to the broader area of microbial pathogenesis and cell signalling in mammalian cells.
专性细胞内病原体建立有效的感染依赖于对细胞防御的破坏。细胞凋亡，即程序性细胞死亡，是后生动物细胞的一种特性，在抑制入侵生物和病毒的增殖中起关键作用，从而保护未感染的细胞并限制对宿主生物体的损害。毫不奇怪，对细胞凋亡机制的操控在几种细胞内病原体的发病机制中起着关键作用。弓形虫，可以说是最成功的原生动物病原体之一，已经进化出多种策略来抑制凋亡级联反应的启动和传播。几个研究小组最近的工作表明，在沿其不同途径抑制细胞凋亡的机制方面有着极高的复杂性。这种能力很大程度上似乎集中在对宿主转录的操控上，特别是对参与促生存/抗凋亡反应的基因的操控，有效地将受感染细胞转变为高度抗凋亡状态。这些观察结果的影响不仅限于弓形虫生物学，还扩展到微生物发病机制和哺乳动物细胞信号传导的更广泛领域。
