{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,30]],"date-time":"2026-09-30T05:01:33Z","timestamp":1790744493717,"version":"4.1.0"},"reference-count":67,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2026,9,30]],"date-time":"2026-09-30T00:00:00Z","timestamp":1790726400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["82503151, 82371764"],"award-info":[{"award-number":["82503151, 82371764"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100003392","name":"Natural Science Foundation of Fujian Province","doi-asserted-by":"publisher","award":["2026J002006, 2025J08328, 2022J011404"],"award-info":[{"award-number":["2026J002006, 2025J08328, 2022J011404"]}],"id":[{"id":"10.13039\/501100003392","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100016808","name":"Natural Science Foundation of Xiamen Municipality","doi-asserted-by":"publisher","award":["3502Z202571070"],"award-info":[{"award-number":["3502Z202571070"]}],"id":[{"id":"10.13039\/100016808","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Cell. Infect. Microbiol."],"abstract":"<jats:sec>\n                    <jats:title>Introduction<\/jats:title>\n                    <jats:p>\n                      <jats:italic>Listeria monocytogenes<\/jats:italic>\n                      (\n                      <jats:italic>L. monocytogenes<\/jats:italic>\n                      ) is an intracellular bacterial pathogen that requires coordinated innate and adaptive immune responses for effective clearance. However, the epigenetic mechanisms governing host defense against\n                      <jats:italic>L. monocytogenes<\/jats:italic>\n                      remain poorly understood.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>\n                      JMJD2D-deficient mice and wild-type littermates were infected with\n                      <jats:italic>L. monocytogenes<\/jats:italic>\n                      to assess host susceptibility, bacterial burdens, tissue damage, and survival. Bone marrow-derived macrophages (BMDMs) and peritoneal macrophages (PMs) were isolated for\n                      <jats:italic>in vitro<\/jats:italic>\n                      infection assays. Molecular mechanisms were investigated in macrophages using siRNA-mediated knockdown, luciferase reporter assays, co-immunoprecipitation (Co-IP) and chromatin immunoprecipitation (ChIP).\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      JMJD2D deficiency markedly increased host susceptibility to\n                      <jats:italic>L. monocytogenes<\/jats:italic>\n                      infection, resulting in elevated bacterial burdens, aggravated tissue damage, and reduced survival. Mechanistically, JMJD2D promoted NOD2-associated innate sensing and enhanced IL-12b transcription, accompanied by reduced H3K9me3 enrichment at the IL-12b promoter and cooperation with c-Rel. JMJD2D deficiency was associated with reduced IL-12p70 secretion and impaired macrophage bactericidal activity. Furthermore, JMJD2D contributed to coordinated macrophage and CD8\n                      <jats:sup>+<\/jats:sup>\n                      T cell responses, as JMJD2D promoted IL-12b expression and IL-12p70 production in macrophages, while IFN\u03b3 enhanced macrophage IL-12b expression through the IFNGR2-JAK2-STAT1 pathway. Notably, the catalytic activity of JMJD2D contributed substantially to the full induction of\n                      <jats:italic>L. monocytogenes<\/jats:italic>\n                      -induced IL-12b expression and inflammatory responses in macrophages.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Discussion<\/jats:title>\n                    <jats:p>\n                      These findings identify JMJD2D as an epigenetic regulator of macrophage IL-12b expression and IL-12p70 production, and support its involvement in coordinated macrophage and CD8\n                      <jats:sup>+<\/jats:sup>\n                      T cell responses during\n                      <jats:italic>L. monocytogenes<\/jats:italic>\n                      infection. Our findings further suggest that the JMJD2D-IL-12b\/IL-12p70-IFN\u03b3 regulatory axis contributes to host antimicrobial immunity and provide a basis for further investigation of JMJD2D as a potential modulator of antibacterial immune responses.\n                    <\/jats:p>\n                  <\/jats:sec>","DOI":"10.3389\/fcimb.2026.1901735","type":"journal-article","created":{"date-parts":[[2026,9,30]],"date-time":"2026-09-30T04:48:37Z","timestamp":1790743717000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":0,"title":["Histone demethylase JMJD2D promotes macrophage IL-12b expression and contributes to host defense against Listeria monocytogenes infection"],"prefix":"10.3389","volume":"16","author":[{"given":"Yilin","family":"Hong","sequence":"first","affiliation":[{"name":"Xiamen Key Laboratory of Traditional Chinese Medicine Bio-engineering, School of Pharmacy, Xiamen Medical College","place":["Xiamen, Fujian, China"]},{"name":"State Key Laboratory of Cellular Stress Biology, Innovation Center for Cell Biology, School of Life Sciences, Xiamen University, Xiamen","place":["Fujian, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hanshi","family":"Guo","sequence":"additional","affiliation":[{"name":"State Key Laboratory of Cellular Stress Biology, Innovation Center for Cell Biology, School of Life Sciences, Xiamen University, Xiamen","place":["Fujian, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Bei","family":"Li","sequence":"additional","affiliation":[{"name":"Ordos Center for Disease Control and Prevention","place":["Ordos, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jing","family":"Jin","sequence":"additional","affiliation":[{"name":"State Key Laboratory of Cellular Stress Biology, Innovation Center for Cell Biology, School of Life Sciences, Xiamen University, Xiamen","place":["Fujian, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yang","family":"Zhao","sequence":"additional","affiliation":[{"name":"State Key Laboratory of Cellular Stress Biology, Innovation Center for Cell Biology, School of Life Sciences, Xiamen University, Xiamen","place":["Fujian, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Junjie","family":"Zhang","sequence":"additional","affiliation":[{"name":"State Key Laboratory of Cellular Stress Biology, Innovation Center for Cell Biology, School of Life Sciences, Xiamen University, Xiamen","place":["Fujian, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jingna","family":"Yuan","sequence":"additional","affiliation":[{"name":"State Key Laboratory of Cellular Stress Biology, Innovation Center for Cell Biology, School of Life Sciences, Xiamen University, Xiamen","place":["Fujian, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xiaochun","family":"Xia","sequence":"additional","affiliation":[{"name":"Department of Public Health and Medical Technology, Xiamen Medical College","place":["Xiamen, Fujian, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chundong","family":"Yu","sequence":"additional","affiliation":[{"name":"State Key Laboratory of Cellular Stress Biology, Innovation Center for Cell Biology, School of Life Sciences, Xiamen University, Xiamen","place":["Fujian, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2026,9,30]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","first-page":"2271","DOI":"10.4049\/jimmunol.1301914","article-title":"IRF4 in dendritic cells inhibits IL-12 production and controls Th1 immune responses against Leishmania major","volume":"192","author":"Akbari","year":"2014","journal-title":"J. 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