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.
State Key Laboratory for Animal Disease Control and Prevention, Lanzhou Veterinary Research Institute, Chinese Academy of Agricultural Sciences, College of Veterinary Medicine, Lanzhou University, Lanzhou 730000, China.
Int J Mol Sci. 2024 Oct 19;25(20):11262. doi: 10.3390/ijms252011262.
is a widely spread opportunistic pathogen that can infect nearly all warm-blooded vertebrates and cause serious toxoplasmosis in immunosuppressed animals and patients. However, the relationship between the host's innate immune system and effector proteins is poorly understood, particularly with regard to how effectors antagonize cGAS-STING signaling during infection. In this study, the ROP5 from the PRU strain of was found to promote cGAS-STING-mediated immune responses. Mechanistically, ROP5 interacted with STING through predicted domain 2 and modulated cGAS-STING signaling in a predicted domain 3-dependent manner. Additionally, ROP5 strengthened cGAS-STING signaling by enhancing the K63-linked ubiquitination of STING. Consistently, ROP5 deficient PRU (PRUΔROP5) induced fewer type I IFN-related immune responses and replicated faster than the parental strain in RAW264.7 cells. Taken together, this study provides new insights into the mechanism by which ROP5 regulates infection and provides new clues for strategies to prevent and control toxoplasmosis.
刚地弓形虫是一种广泛传播的机会性病原体，几乎可以感染所有温血脊椎动物，并在免疫抑制的动物和患者中引起严重的弓形体病。然而，宿主先天免疫系统和效应蛋白之间的关系还了解甚少，特别是关于效应蛋白如何在感染过程中拮抗 cGAS-STING 信号。在这项研究中，发现 PRU 株的 ROP5 促进 cGAS-STING 介导的免疫反应。在机制上，ROP5 通过预测结构域 2 与 STING 相互作用，并以预测结构域 3 依赖的方式调节 cGAS-STING 信号。此外，ROP5 通过增强 STING 的 K63 连接泛素化来增强 cGAS-STING 信号。一致地，ROP5 缺陷型 PRU（PRUΔROP5）在 RAW264.7 细胞中比亲本株系诱导更少的 I 型 IFN 相关免疫反应和更快的复制。总之，这项研究为 ROP5 调节弓形体感染的机制提供了新的见解，并为预防和控制弓形体病提供了新的线索。
