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This condition arises from an increased susceptibility to chronic\n              <jats:italic>Brucella<\/jats:italic>\n              infection, a significant clinical challenge. One key factor contributing to chronic neurobrucellosis is the regulation of microglial apoptosis by\n              <jats:italic>Brucella<\/jats:italic>\n              ; however, the exact molecular mechanisms remain largely unresolved. In this study, human microglial clone 3 (HMC3) cells were infected with\n              <jats:italic>Brucella suis<\/jats:italic>\n              vaccine strain S2 (\n              <jats:italic>B. suis<\/jats:italic>\n              S2) at varying multiplicity of infection (MOI) and durations to assess its effects on the IRE1\/caspase-12\/caspase-3 signaling pathway. Following the suppression of this pathway by\n              <jats:italic>B. suis<\/jats:italic>\n              S2, calreticulin (CALR) was identified through ubiquitin-modified proteomics (data accessible via ProteomeXchange, identifier PXD056006). To further investigate, CALR-overexpression and knockdown HMC3 cell lines were infected with\n              <jats:italic>B. suis<\/jats:italic>\n              S2 to elucidate the mechanism by which\n              <jats:italic>B. suis<\/jats:italic>\n              S2 inhibits apoptosis in HMC3 cells. In conclusion, our findings demonstrate that\n              <jats:italic>B. suis<\/jats:italic>\n              S2 suppresses HMC3 cell apoptosis via the IRE1\/caspase-12\/caspase-3 pathway by modulating CALR ubiquitination. This study provides a theoretical basis for exploring the mechanisms of neurobrucellosis and offers insights into its clinical treatment.\n            <\/jats:p>\n            <jats:sec>\n              <jats:title>IMPORTANCE<\/jats:title>\n              <jats:p>\n                Neurobrucellosis is a severe complication impacting the central nervous system (CNS) due to neurological deficits caused by\n                <jats:italic>Brucella<\/jats:italic>\n                , with primary clinical features including meningitis, encephalitis, brain abscesses, and demyelinating lesions. These nonspecific symptoms often lead to misdiagnosis or delayed diagnosis, increasing the risk of recurrent or chronic neurobrucellosis infections. Consequently, persistent infection and relapse are critical challenges in the clinical management of neurobrucellosis, which are closely linked to\n                <jats:italic>Brucella<\/jats:italic>\n                \u2019s survival and replication within microglia. Interestingly,\n                <jats:italic>Brucella<\/jats:italic>\n                may inhibit microglia apoptosis by mitigating endoplasmic reticulum (ER) stress, though the precise molecular mechanisms remain largely unexplored. Thus, this study will elucidate the specific mechanisms by which\n                <jats:italic>Brucella<\/jats:italic>\n                suppresses microglial apoptosis and provide deeper insights into the molecular pathogenesis and clinical treatment of neurobrucellosis.\n              <\/jats:p>\n            <\/jats:sec>\n          <\/jats:sec>","DOI":"10.1128\/msphere.00941-24","type":"journal-article","created":{"date-parts":[[2025,2,28]],"date-time":"2025-02-28T14:00:43Z","timestamp":1740751243000},"update-policy":"https:\/\/doi.org\/10.1128\/asmj-crossmark-policy-page","source":"Crossref","is-referenced-by-count":2,"title":["<i>Brucella suis<\/i>\n            S2 strain inhibits IRE1\/caspase-12\/caspase-3 pathway-mediated apoptosis of microglia HMC3 by affecting the ubiquitination of CALR"],"prefix":"10.1128","volume":"10","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-1679-2650","authenticated-orcid":true,"given":"Zhao","family":"Wang","sequence":"first","affiliation":[{"name":"Department of Experimental Surgery, The Second Affiliated Hospital of Air Force Medical University","place":["Xi'an, China"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yanbai","family":"Wang","sequence":"additional","affiliation":[{"name":"Department of Neurology, The General Hospital of Ningxia Medical University","place":["Yinchuan, China"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Shulong","family":"Yang","sequence":"additional","affiliation":[{"name":"Department of Orthopedics, The People\u2019s Hospital of Wuhai","place":["Wuhai, 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