Toxoplasma gondii ROP18I inhibits host innate immunity through cGAS-STING signaling
Toxoplasma gondii ROP18I inhibits host innate immunity through cGAS-STING signaling
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DOI：
10.1096/fj.202101347r
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发表时间：
2022-02-01
期刊：
影响因子：
4.8
通讯作者：
Peng, Hongjuan
中科院分区：
文献类型：
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作者：
Chen, Min;Yao, Lijie;Peng, Hongjuan
弓形虫是一种机会性原虫，广泛感染人类和其他温血动物。I型干扰素（IFN）如IFN-α/β参与cGAS-STING信号传导以抵抗T.弓形虫感染我们在RAW264.7细胞中发现，T.弓形虫毒力因子TgROP 18（I）通过与干扰素调节因子3（IRF 3）相互作用抑制IFN-β的产生。此外，TgROP 18（I）与p62和肿瘤坏死因子受体相关因子6（TRAF 6）相互作用，这导致TRAF 6-p62相互作用的抑制和p62的磷酸化。此外，TgROP 18 1限制了泛素的募集。p62和微管相关蛋白轻链3（LC 3）的寄生虫空泡膜（PVM）在IFN-γ刺激的小鼠细胞系L929细胞。在IFN-γ刺激的人细胞中，TgROP 18（I）限制了PVM与泛素、p62和LC 3的装饰，并分别与TRAF 2、TRAF 6和p62结合。结果，TgROP 18（I）导致在鼠和人细胞中成功的寄生复制。总的来说，我们的研究揭示了TgROP 18（I）在T.弓形虫感染引起寄生虫免疫逃逸。
Toxoplasma gondii is an opportunistic protozoan, which widely infects humans and other warm-blooded animals. The type I interferon (IFN) such as IFN-alpha/beta is involved in cGAS-STING signaling to resist T. gondii infection. We found in RAW264.7 cells, that T. gondii virulence factor TgROP18(I), inhibited IFN-beta production through interacting with interferon regulatory factor 3 (IRF3). Besides, TgROP18(I) interacted with p62 and Tumor Necrotic Factor Receptor Associated Factor 6 (TRAF6), which resulted in the inhibition of TRAF6-p62 interaction, and phosphorylation of p62. Furthermore, TgROP18 1 restricted the recruitment of ubiquitin. p62 and microtubule-associated protein light chain 3 (LC3) to the parasitophorous vacuole membrane (PVM) in IFN-gamma-stimulated murine cell line L929 cells. In IFN-gamma-stimulated human cells, TgROP18(I) restricted the decoration of PVM with ubiquitin, p62, and LC3, and bound with TRAF2, TRAF6, and p62, respectively. As a result, TgROP18(I) led to a successful parasitic replication in murine and human cells. Collectively, our study revealed the function of TgROP18(I) in suppressing host type I interferon responses in T. gondii infection for parasitic immune escape.