Department of Pathogen Biology, Guangdong Provincial Key Laboratory of Tropical Disease Research, School of Public Health, Southern Medical University, Guangzhou, Guangdong Province, 510515, China.
Int J Biol Sci. 2017 Sep 5;13(9):1126-1137. doi: 10.7150/ijbs.21247. eCollection 2017.
The obligate intracellular parasite, , manipulates the cytoskeleton of its host cells to facilitate infection. A significant rearrangement of host cell vimentin around parasitophorous vacuoles is observed during the course of infection. ROP18 (ROP18) is a serine-threonine kinase secreted by rhoptry and a major virulence factor; however, the mechanisms by which this kinase modulates host factors remain poorly understood. Different and dynamic patterns of vimentin solubility, phosphorylation, and expression levels were observed in host cells infected with strain RH and RH Δ strains, suggesting that ROP18 contributes to the regulation of these dynamic patterns. Additionally, host cell vimentin was demonstrated to interact with and be phosphorylated by ROP18. A significant increase in infection rate was observed in vimentin knockout human brain microvessel endothelial cells (HBMEC), while vimentin knockout or knock down in host cells had no impact on parasite proliferation and egress. These results indicate that host cell vimentin can inhibit invasion. Interestingly, western blotting of different mouse tissues indicated that the lowest vimentin expression level was present in the brain, which may explain the mechanism underlying the nervous system tropism of , and the phenomenon of huge cyst burdens developing in the mouse brain during chronic infection.
专性细胞内寄生虫 操纵宿主细胞的细胞骨架以促进感染。在感染过程中，观察到宿主细胞中间丝围绕 滋养体空泡的显著重排。ROP18（ROP18）是一种由 泡状密螺旋体分泌的丝氨酸-苏氨酸激酶，是一种主要的毒力因子；然而，这种激酶调节宿主因子的机制仍知之甚少。用 RH 株和 RH Δ株感染的宿主细胞中观察到中间丝溶解性、磷酸化和表达水平的不同和动态模式，表明 ROP18 有助于调节这些动态模式。此外，宿主细胞中间丝被证明与 ROP18 相互作用并被其磷酸化。在中间丝敲除的人脑血管内皮细胞（HBMEC）中， 感染率显著增加，而在宿主细胞中敲除或敲低中间丝对寄生虫增殖和逸出没有影响。这些结果表明宿主细胞中间丝可以抑制 入侵。有趣的是，对不同小鼠组织的 Western 印迹分析表明，大脑中中间丝的表达水平最低，这可能解释了 对神经系统的嗜性以及在慢性感染期间小鼠大脑中出现巨大囊泡负担的现象的机制。
