{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,17]],"date-time":"2026-06-17T11:51:39Z","timestamp":1781697099589,"version":"3.54.5"},"reference-count":77,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2026,6,9]],"date-time":"2026-06-09T00:00:00Z","timestamp":1780963200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Immunol."],"abstract":"<jats:p>\n                    IL-10, an anti-inflammatory cytokine, plays a crucial role in limiting immune responses to pathogens, preventing host damage. However, the mechanisms underlying\n                    <jats:italic>Brucella<\/jats:italic>\n                    -mediated IL-10 production remain incompletely understood. In this study, we demonstrate that the proline racemase protein A (PrpA) of\n                    <jats:italic>Brucella melitensis<\/jats:italic>\n                    M5\u201390 induces macrophages to secrete IL-10 by activating the Tpl2-ERK signaling pathway, thereby promoting chronic infection. Moreover,\n                    <jats:italic>Tpl2<\/jats:italic>\n                    deletion impairs macrophage bactericidal ability, accompanied by reduced TNF-\u03b1, IL-1\u03b2 and IL-10 levels. Additionally, Trp309, Glu103, and Glu129 of PrpA participate in interaction with Tpl2, but these residues do not influence PrpA-mediated IL-10 production in macrophages.\n                    <jats:italic>PrpA<\/jats:italic>\n                    deletion enhances IFN-\u03b3 levels, specific anti-\n                    <jats:italic>Brucella<\/jats:italic>\n                    IgG, and CD4+ and CD8+ T cell numbers in mice. Furthermore, the\n                    <jats:italic>Brucella melitensis<\/jats:italic>\n                    M5\u201390\n                    <jats:italic>prpA<\/jats:italic>\n                    mutant provides higher protection than the parental strain against virulent\n                    <jats:italic>Brucella melitensis<\/jats:italic>\n                    M28 infection in mice. Our findings suggest that\n                    <jats:italic>Brucella<\/jats:italic>\n                    PrpA promotes IL-10 secretion by macrophages through Tpl2 activation for bacterial survival and persistent infection, making the\n                    <jats:italic>Brucella melitensis<\/jats:italic>\n                    M5\u201390\n                    <jats:italic>prpA<\/jats:italic>\n                    mutant a promising vaccine for enhanced protection.\n                  <\/jats:p>","DOI":"10.3389\/fimmu.2026.1808256","type":"journal-article","created":{"date-parts":[[2026,6,9]],"date-time":"2026-06-09T04:28:39Z","timestamp":1780979319000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":0,"title":["Brucella proline racemase protein A targets Tpl2 to promote IL-10 secretion for establishment of chronic infection"],"prefix":"10.3389","volume":"17","author":[{"given":"Huan","family":"Zhang","sequence":"first","affiliation":[{"name":"School of Animal Science and Technology, Shihezi University","place":["Xinjiang, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xueyu","family":"Tao","sequence":"additional","affiliation":[{"name":"School of Animal Science and Technology, Shihezi University","place":["Xinjiang, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yuanzhi","family":"Wang","sequence":"additional","affiliation":[{"name":"School of Medicine, Shihezi University","place":["Xinjiang, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yueli","family":"Wang","sequence":"additional","affiliation":[{"name":"School of Medicine, Shihezi University","place":["Xinjiang, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Huilin","family":"Hou","sequence":"additional","affiliation":[{"name":"School of Animal Science and Technology, Shihezi University","place":["Xinjiang, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xiaoyu","family":"Deng","sequence":"additional","affiliation":[{"name":"School of Animal Science and Technology, Shihezi University","place":["Xinjiang, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zhenyu","family":"Xu","sequence":"additional","affiliation":[{"name":"School of Animal Science and Technology, Shihezi University","place":["Xinjiang, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xujin","family":"Xia","sequence":"additional","affiliation":[{"name":"Center for Animal Disease Control and Diagnosis in Bayinggolin Mongol Autonomus Prefecture","place":["Xinjiang, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mingguo","family":"Xu","sequence":"additional","affiliation":[{"name":"School of Animal Science and Technology, Shihezi University","place":["Xinjiang, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zhen","family":"Wang","sequence":"additional","affiliation":[{"name":"School of Animal Science and Technology, Shihezi University","place":["Xinjiang, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Changsuo","family":"Zhang","sequence":"additional","affiliation":[{"name":"Tecon Biological Co. 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