Artemisinin Research Center, Guangzhou University of Chinese Medicine, Guangzhou, Guangdong, China.
State Key Laboratory of Pathogen and Biosecurity, Beijing Institute of Microbiology and Epidemiology, Beijing, China.
Microbiol Spectr. 2024 Apr 2;12(4):e0369523. doi: 10.1128/spectrum.03695-23. Epub 2024 Feb 15.
(), the causative agent of Rocky Mountain spotted fever (RMSF), is the most pathogenic member among spp. Previous studies have shown that tripartite motif-containing 56 (TRIM56) E3 ligase-induced ubiquitination of STING is important for cytosolic DNA sensing and type I interferon production to induce anti-DNA viral immunity, but whether it affects intracellular replication of remains uncharacterized. Here, we investigated the effect of TRIM56 on HeLa and THP-1 cells infected with . We found that the expression of TRIM56 was upregulated in the -infected cells, and the overexpression of TRIM56 inhibited the intracellular replication of , while replication was enhanced in the TRIM56-silenced host cells with the reduced phosphorylation of IRF3 and STING and the increased production of interferon-β. In addition, the mutation of the TRIM56 E3 ligase catalytic site impairs the inhibitory function against in HeLa cells. Altogether, our study discovers that TRIM56 is a host restriction factor of by regulating the cGAS-STING-mediated signaling pathway. This study gives new evidence for the role of TRIM56 in the innate immune response against intracellular bacterial infection and provides new therapeutic targets for RMSF.
Given that () is the most pathogenic member within the genus and serves as the causative agent of Rocky Mountain spotted fever, there is a growing need to explore host targets. In this study, we examined the impact of host TRIM56 on infection in HeLa and THP-1 cells. We observed a significant upregulation of TRIM56 expression in -infected cells. Remarkably, the overexpression of TRIM56 inhibited the intracellular replication of , while silencing TRIM56 enhanced bacterial replication accompanied by reduced phosphorylation of IRF3 and STING, along with increased interferon-β production. Notably, the mutation of the TRIM56's E3 ligase catalytic site did not impede replication in HeLa cells. Collectively, our findings provide novel insights into the role of TRIM56 as a host restriction factor against through the modulation of the cGAS-STING signaling pathway.
（），落矶山斑点热（RMSF）的病原体，是 spp 中最具致病性的成员。先前的研究表明，三结构域含 56（TRIM56）E3 连接酶诱导 STING 的泛素化对于细胞质 DNA 感应和 I 型干扰素产生以诱导抗 DNA 病毒免疫很重要，但它是否影响仍未被描述。在这里，我们研究了 TRIM56 对感染的 HeLa 和 THP-1 细胞的影响。我们发现，在感染的细胞中 TRIM56 的表达上调，而 TRIM56 的过表达抑制了 的细胞内复制，而宿主细胞中 TRIM56 的沉默导致 IRF3 和 STING 的磷酸化减少，干扰素-β的产生增加，从而增强了 复制。此外，TRIM56 E3 连接酶催化位点的突变会损害其在 HeLa 细胞中对 的抑制功能。总之，我们的研究发现 TRIM56 通过调节 cGAS-STING 介导的信号通路成为 的宿主限制因子。这项研究为 TRIM56 在先天免疫反应中对细胞内细菌感染的作用提供了新的证据，并为落矶山斑点热提供了新的治疗靶点。
鉴于（）是属内最具致病性的成员，也是落矶山斑点热的病原体，因此越来越需要探索宿主靶标。在这项研究中，我们研究了宿主 TRIM56 对 HeLa 和 THP-1 细胞中感染的影响。我们观察到感染细胞中 TRIM56 的表达显著上调。值得注意的是，TRIM56 的过表达抑制了 的细胞内复制，而 TRIM56 的沉默增强了细菌的复制，同时伴随着 IRF3 和 STING 的磷酸化减少，以及干扰素-β的产生增加。值得注意的是，TRIM56 的 E3 连接酶催化位点突变并没有阻止 HeLa 细胞中 的复制。总的来说，我们的发现提供了新的见解，即 TRIM56 通过调节 cGAS-STING 信号通路作为一种宿主限制因子对抗。
