细胞凋亡是细胞死亡的精细编程过程,其中细胞无声地分解并积极参与多种操作,例如免疫反应,分化,和细胞生长。它可以通过三种主要途径启动:外在,穿孔素颗粒酶,以及内在的,最终导致几种负责撕毁细胞的蛋白质的激活。另一方面,细胞凋亡代表了生活在细胞内并与它们保持强烈依赖性的病原体的考验;因此,他们已经进化出多种策略来代表他们操纵宿主细胞凋亡。广泛的文献表明,不同的细胞内细菌,真菌,寄生虫可以干扰宿主细胞凋亡机制的大多数步骤,从而抑制或诱导细胞凋亡。的确,抑制细胞凋亡被认为是许多细胞内病原体共享的毒力特性,以确保生产性复制。一些病原体通过干扰细胞外信号或转导途径的感知而在早期进行干预。其他人感知细胞应激或靶向Bcl-2家族或半胱天冬酶的凋亡调节蛋白。在许多情况下,导致干扰宿主细胞凋亡级联的确切分子机制仍然未知。然而,已经进行了大量的研究来阐明细胞内病原体用来调节宿主细胞死亡的策略。在这次审查中,我们总结了细胞凋亡激活的主要途径,并介绍了不同细菌使用的几个过程,真菌,和寄生虫来调节其宿主细胞的凋亡。
Apoptosis is a finely programmed process of cell death in which cells silently dismantle and actively participate in several operations such as immune response, differentiation, and cell growth. It can be initiated by three main pathways: the extrinsic, the perforin granzyme, and the intrinsic that culminate in the activation of several proteins in charge of tearing down the cell. On the other hand, apoptosis represents an ordeal for pathogens that live inside cells and maintain a strong dependency with them; thus, they have evolved multiple strategies to manipulate host cell apoptosis on their behalf. It has been widely documented that diverse intracellular bacteria, fungi, and parasites can interfere with most steps of the host cell apoptotic machinery to inhibit or induce apoptosis. Indeed, the inhibition of apoptosis is considered a virulence property shared by many intracellular pathogens to ensure productive replication. Some pathogens intervene at an early stage by interfering with the sensing of extracellular signals or transduction pathways. Others sense cellular stress or target the apoptosis regulator proteins of the Bcl-2 family or caspases. In many cases, the exact molecular mechanisms leading to the interference with the host cell apoptotic cascade are still unknown. However, intense research has been conducted to elucidate the strategies employed by intracellular pathogens to modulate host cell death. In this review, we summarize the main routes of activation of apoptosis and present several processes used by different bacteria, fungi, and parasites to modulate the apoptosis of their host cells.