Toxoplasma gondii SAG1 targeting host cell S100A6 for parasite invasion and host immunity.
Toxoplasma gondii SAG1 targeting host cell S100A6 for parasite invasion and host immunity.
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弓形虫SAG1靶向宿主细胞S100A6用于寄生虫入侵和宿主免疫
DOI：
10.1016/j.isci.2021.103514
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发表时间：
2021-12-17
期刊：
影响因子：
5.8
通讯作者：
Peng HJ
中科院分区：
文献类型：
--
作者：
Zhou LJ;Peng J;Chen M;Yao LJ;Zou WH;He CY;Peng HJ
弓形虫表面抗原1(TgSAG1)是一种速殖子表面蛋白，在弓形虫感染和宿主细胞免疫调节中起重要作用。然而，TgSAG1如何调控这些过程仍未阐明。我们利用生物素连接酶-TurboID与TgSAG1的融合来鉴定与TgSAG1相互作用的宿主蛋白，当弓形虫附着在宿主细胞上时，S100A6与TgSAG1是共定位的。S100A6基因敲除或封闭其功能表位均可抑制寄生虫入侵。同时，S100A6在宿主细胞中的过表达促进了弓形虫的感染。进一步验证了TgSAG1能抑制弓形虫侵袭过程中宿主细胞波形蛋白与S100A6的细胞骨架相互作用。作为免疫原，TgSAG1可通过S100A6-α/PKC-θ-NF-κB信号通路促进肿瘤坏死因子-α的分泌。综上所述，我们的发现揭示了TgSAG1在寄生虫入侵和宿主免疫调节中的作用机制。TgSAG1与宿主蛋白S100A6相互作用，进而调控弓形虫感染过程中与S100A6结合的波形蛋白TgSAG1通过S100A6-Vimentin/PKCα-θ-NF-κB信号通路调节肿瘤坏死因子DNA的分泌分子生物学；免疫应答；寄生虫学
Toxoplasma gondii surface antigen 1 (TgSAG1) is a surface protein of tachyzoites, which plays a crucial role in toxoplasma gondii infection and host cell immune regulation. However, how TgSAG1 regulates these processes remains elucidated. We utilized the biotin ligase -TurboID fusion with TgSAG1 to identify the host proteins interacting with TgSAG1, and identified that S100A6 was co-localized with TgSAG1 when T. gondii 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 T. gondii infection. We further verified that TgSAG1 could inhibit the interaction of host cell vimentin with S100A6 for cytoskeleton organization during T. gondii invasion. As an immunogen, TgSAG1 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 TgSAG1 functioned in parasitic invasion and host immune regulation. TgSAG1 interacts with host protein S100A6 then regulates T. gondii infection TgSAG1 could regulate binding vimentin with S100A6 during T. gondii infection TgSAG1 regulate TNFα secretion through S100A6-vimentin/PKCθ-NF-κB signaling pathway Molecular biology; Immune response; Parasitology
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