Jiangsu Key Laboratory of Zoonosis, Jiangsu Co-Innovation Center for Prevention and Control of Important Animal Infectious Diseases and Zoonosis, Institute of Comparative Medicine, College of Veterinary Medicine, Yangzhou University, Yangzhou 225009, China.
Joint International Research Laboratory of Agriculture and Agri-Product Safety, The Ministry of Education of China, Yangzhou University, Yangzhou 225009, China.
Cells. 2023 Jul 15;12(14):1862. doi: 10.3390/cells12141862.
cGAS-STING signaling is a major pathway in inducing type Ⅰ IFN, which plays a crucial role in the defense against infection. In contrast, develops multiple strategies to counteract the host defense, causing serious diseases in a wide range of hosts. Here, we demonstrate that rhoptry protein 16 (ROP16) dampens type I interferon signaling via the inhibition of the cGAS (cyclic GMP-AMP synthase) pathway through the polyubiquitination of STING. Mechanistically, ROP16 interacts with STING through the SignalP domain and inhibits the K63-linked ubiquitination of STING in an NLS (nuclear localization signal)-domain-dependent manner. Consequently, knocking out the ROP16 in PRU tachyzoites promotes the STING-mediated production of type I IFNs and limits the replication of Together, these findings describe a distinct pathway where exploits the ubiquitination of STING to evade host anti-parasite immunity, revealing new insights into the interaction between the host and parasites.
cGAS-STING 信号通路是诱导 I 型干扰素的主要途径，在抵御感染中起着至关重要的作用。相比之下，寄生虫会发展多种策略来对抗宿主防御，从而导致广泛宿主的严重疾病。在这里，我们证明 顶复体蛋白 16（ROP16）通过多泛素化 STING 抑制 cGAS（环鸟苷酸-腺苷酸合酶）途径来抑制 I 型干扰素信号。在机制上，ROP16 通过 SignalP 结构域与 STING 相互作用，并以 NLS（核定位信号）结构域依赖的方式抑制 STING 的 K63 连接泛素化。因此，敲除 PRU 速殖子中的 ROP16 会促进 STING 介导的 I 型 IFNs 的产生，并限制 的复制。总之，这些发现描述了一种独特的途径，即寄生虫利用 STING 的泛素化来逃避宿主抗寄生虫免疫，揭示了宿主和寄生虫之间相互作用的新见解。
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