Hakimi Mohamed-Ali, Olias Philipp, Sibley L David
Institute for Advanced Biosciences, Team Host-Pathogen Interactions and Immunity to Infection, INSERM U1209, CNRS UMR 5309, Université Grenoble Alpes, Grenoble, France.
Department of Molecular Microbiology, Washington University School of Medicine, St. Louis, Missouri, USA.
Clin Microbiol Rev. 2017 Jul;30(3):615-645. doi: 10.1128/CMR.00005-17.
Early electron microscopy studies revealed the elaborate cellular features that define the unique adaptations of apicomplexan parasites. Among these were bulbous rhoptry (ROP) organelles and small, dense granules (GRAs), both of which are secreted during invasion of host cells. These early morphological studies were followed by the exploration of the cellular contents of these secretory organelles, revealing them to be comprised of highly divergent protein families with few conserved domains or predicted functions. In parallel, studies on host-pathogen interactions identified many host signaling pathways that were mysteriously altered by infection. It was only with the advent of forward and reverse genetic strategies that the connections between individual parasite effectors and the specific host pathways that they targeted finally became clear. The current repertoire of parasite effectors includes ROP kinases and pseudokinases that are secreted during invasion and that block host immune pathways. Similarly, many secretory GRA proteins alter host gene expression by activating host transcription factors, through modification of chromatin, or by inducing small noncoding RNAs. These effectors highlight novel mechanisms by which has learned to harness host signaling to favor intracellular survival and will guide future studies designed to uncover the additional complexity of this intricate host-pathogen interaction.
早期的电子显微镜研究揭示了一些精细的细胞特征，这些特征定义了顶复门寄生虫独特的适应性。其中包括球状的棒状体（ROP）细胞器和小的致密颗粒（GRA），这两种结构在入侵宿主细胞时都会分泌。在这些早期的形态学研究之后，人们对这些分泌细胞器的细胞内容物进行了探索，发现它们由高度不同的蛋白质家族组成，几乎没有保守结构域或预测功能。与此同时，对宿主-病原体相互作用的研究确定了许多被感染神秘改变的宿主信号通路。直到正向和反向遗传策略出现，单个寄生虫效应器与其靶向的特定宿主通路之间的联系才最终变得清晰。目前已知的寄生虫效应器包括入侵期间分泌并阻断宿主免疫通路的ROP激酶和假激酶。同样，许多分泌性GRA蛋白通过激活宿主转录因子、修饰染色质或诱导小非编码RNA来改变宿主基因表达。这些效应器突出了寄生虫学会利用宿主信号以利于细胞内存活的新机制，并将指导未来旨在揭示这种复杂宿主-病原体相互作用更多复杂性的研究。
