Zhou Li-Juan, Peng Jiao, Chen Min, Yao Li-Jie, Zou Wei Hao, He Cynthia Y, Peng Hong-Juan
Department of Pathogen Biology, Guangdong Provincial Key Laboratory of Tropical Disease Research, School of Public Health, Southern Medical University, Guangzhou, Guangdong Province 510515, P R China.
Department of Biological Sciences, National University of Singapore, Singapore 119077, Singapore.
iScience. 2021 Nov 26;24(12):103514. doi: 10.1016/j.isci.2021.103514. eCollection 2021 Dec 17.
surface antigen 1 (SAG1) is a surface protein of tachyzoites, which plays a crucial role in infection and host cell immune regulation. However, how SAG1 regulates these processes remains elucidated. We utilized the biotin ligase -TurboID fusion with SAG1 to identify the host proteins interacting with SAG1, and identified that S100A6 was co-localized with SAG1 when attached to the host cell. S100A6, either knocking down or blocking its functional epitopes resulted in inhibited parasites invasion. Meanwhile, S100A6 overexpression in host cells promoted infection. We further verified that SAG1 could inhibit the interaction of host cell vimentin with S100A6 for cytoskeleton organization during invasion. As an immunogen, SAG1 could promote the secretion of tumor necrosis factor alpha (TNF-α) through S100A6-Vimentin/PKCθ-NF-κB signaling pathway. In summary, our findings revealed a mechanism for how SAG1 functioned in parasitic invasion and host immune regulation.
表面抗原1（SAG1）是速殖子的一种表面蛋白，在感染和宿主细胞免疫调节中起关键作用。然而，SAG1如何调节这些过程仍有待阐明。我们利用与SAG1融合的生物素连接酶TurboID来鉴定与SAG1相互作用的宿主蛋白，并确定当附着于宿主细胞时，S100A6与SAG1共定位。敲低S100A6或阻断其功能表位均导致寄生虫入侵受到抑制。同时，宿主细胞中S100A6的过表达促进了感染。我们进一步证实，在入侵过程中，SAG1可抑制宿主细胞波形蛋白与S100A6的相互作用以进行细胞骨架组织。作为一种免疫原，SAG1可通过S100A6-波形蛋白/PKCθ-NF-κB信号通路促进肿瘤坏死因子α（TNF-α）的分泌。总之，我们的研究结果揭示了SAG1在寄生虫入侵和宿主免疫调节中发挥作用的机制。
