{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,19]],"date-time":"2026-06-19T18:26:12Z","timestamp":1781893572967,"version":"3.54.5"},"reference-count":39,"publisher":"American Society for Microbiology","issue":"4","license":[{"start":{"date-parts":[[2024,4,2]],"date-time":"2024-04-02T00:00:00Z","timestamp":1712016000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"},{"start":{"date-parts":[[2024,4,2]],"date-time":"2024-04-02T00:00:00Z","timestamp":1712016000000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/journals.asm.org\/non-commercial-tdm-license"}],"funder":[{"name":"Beijing Municipal Natural Science Foundation","award":["5244052"],"award-info":[{"award-number":["5244052"]}]},{"DOI":"10.13039\/501100015976","name":"State Key Laboratory of Pathogen and Biosecurity","doi-asserted-by":"crossref","award":["SKLPBS2216"],"award-info":[{"award-number":["SKLPBS2216"]}],"id":[{"id":"10.13039\/501100015976","id-type":"DOI","asserted-by":"crossref"}]}],"content-domain":{"domain":["journals.asm.org"],"crossmark-restriction":true},"short-container-title":["Microbiol Spectr"],"published-print":{"date-parts":[[2024,4,2]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n          <jats:sec>\n            <jats:title\/>\n            <jats:p>\n              <jats:italic>Rickettsia rickettsii<\/jats:italic>\n              (\n              <jats:italic>R. rickettsii<\/jats:italic>\n              ), the causative agent of Rocky Mountain spotted fever (RMSF), is the most pathogenic member among\n              <jats:italic>Rickettsia<\/jats:italic>\n              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\n              <jats:italic>R. rickettsii<\/jats:italic>\n              remains uncharacterized. Here, we investigated the effect of TRIM56 on HeLa and THP-1 cells infected with\n              <jats:italic>R. rickettsii<\/jats:italic>\n              . We found that the expression of TRIM56 was upregulated in the\n              <jats:italic>R. rickettsii<\/jats:italic>\n              -infected cells, and the overexpression of TRIM56 inhibited the intracellular replication of\n              <jats:italic>R. rickettsii<\/jats:italic>\n              , while\n              <jats:italic>R. rickettsii<\/jats:italic>\n              replication was enhanced in the TRIM56-silenced host cells with the reduced phosphorylation of IRF3 and STING and the increased production of interferon-\u03b2. In addition, the mutation of the TRIM56 E3 ligase catalytic site impairs the inhibitory function against\n              <jats:italic>R. rickettsii<\/jats:italic>\n              in HeLa cells. Altogether, our study discovers that TRIM56 is a host restriction factor of\n              <jats:italic>R. rickettsii<\/jats:italic>\n              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.\n            <\/jats:p>\n          <\/jats:sec>\n          <jats:sec>\n            <jats:title>IMPORTANCE<\/jats:title>\n            <jats:p>\n              Given that\n              <jats:italic>Rickettsia rickettsii<\/jats:italic>\n              (\n              <jats:italic>R. rickettsii<\/jats:italic>\n              ) is the most pathogenic member within the\n              <jats:italic>Rickettsia<\/jats:italic>\n              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\n              <jats:italic>R. rickettsii<\/jats:italic>\n              infection in HeLa and THP-1 cells. We observed a significant upregulation of TRIM56 expression in\n              <jats:italic>R. rickettsii<\/jats:italic>\n              -infected cells. Remarkably, the overexpression of TRIM56 inhibited the intracellular replication of\n              <jats:italic>R. rickettsii<\/jats:italic>\n              , while silencing TRIM56 enhanced bacterial replication accompanied by reduced phosphorylation of IRF3 and STING, along with increased interferon-\u03b2 production. Notably, the mutation of the TRIM56\u2019s E3 ligase catalytic site did not impede\n              <jats:italic>R. rickettsii<\/jats:italic>\n              replication in HeLa cells. Collectively, our findings provide novel insights into the role of TRIM56 as a host restriction factor against\n              <jats:italic>R. rickettsii<\/jats:italic>\n              through the modulation of the cGAS-STING signaling pathway.\n            <\/jats:p>\n          <\/jats:sec>","DOI":"10.1128\/spectrum.03695-23","type":"journal-article","created":{"date-parts":[[2024,2,15]],"date-time":"2024-02-15T13:45:19Z","timestamp":1708004719000},"update-policy":"https:\/\/doi.org\/10.1128\/asmj-crossmark-policy-page","source":"Crossref","is-referenced-by-count":2,"title":["TRIM56-mediated production of type I interferon inhibits intracellular replication of\n            <i>Rickettsia rickettsii<\/i>"],"prefix":"10.1128","volume":"12","author":[{"given":"Ruxi","family":"Cheng","sequence":"first","affiliation":[{"name":"Artemisinin Research Center, Guangzhou University of Chinese Medicine, Guangzhou, Guangdong, China"},{"name":"State Key Laboratory of Pathogen and Biosecurity, Beijing 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