Toxoplasma gondii SAG1 targeting host cell S100A6 for parasite invasion and host immunity
Li-Juan Zhou,
Jiao Peng,
Min Chen,
Li-Jie Yao,
Wei-Hao Zou,
Cynthia Y. He,
Hong-Juan Peng
Affiliations
Li-Juan Zhou
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
Jiao Peng
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
Min Chen
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
Li-Jie Yao
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
Wei-Hao Zou
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
Cynthia Y. He
Department of Biological Sciences, National University of Singapore, Singapore 119077, Singapore
Hong-Juan Peng
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; Corresponding author
Summary: 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.
