TRIM56-mediated production of type I interferon inhibits intracellular replication of .

Unlabelled: (), 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.

Importance: 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.