{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,31]],"date-time":"2026-08-31T14:46:45Z","timestamp":1788187605187,"version":"build-2803163510"},"reference-count":35,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2026,1,5]],"date-time":"2026-01-05T00:00:00Z","timestamp":1767571200000},"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:sec>\n                    <jats:title>Background<\/jats:title>\n                    <jats:p>\n                      Mycobacterium tuberculosis (MTB) evades host immunity and maintains chronic infection, in part by reprogramming macrophage function. The chemokine\n                      <jats:italic>MCP-1<\/jats:italic>\n                      and its receptor\n                      <jats:italic>CCR2<\/jats:italic>\n                      play a key role in attracting monocytes and immunological modulation, but their exact involvement in MTB pathogenesis is unknown.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>\n                      Using the H37Ra-infected mouse model, the expression of MTB virulence marker ESAT-6 and autophagy marker Beclin-1 was assessed. Transcriptome analysis was performed to identify\n                      <jats:italic>CCR2<\/jats:italic>\n                      -related gene expression changes and enriched pathways. In addition, the effects of\n                      <jats:italic>CCR2<\/jats:italic>\n                      antagonists and\n                      <jats:italic>MCP-1<\/jats:italic>\n                      knockdown on macrophage apoptosis, polarization, cytokine production, and immunosuppressive signaling were assessed using Quantitative real-time PCR, ELISA, flow cytometry, immunohistochemistry, immunofluorescence, and western blot.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      <jats:italic>CCR2<\/jats:italic>\n                      inhibition reduced ESAT-6 expression and restored Beclin-1 levels in lung tissue, alleviating inflammation and injury during late-stage infection. Transcriptomic profiling revealed that H37Ra infection activated\n                      <jats:italic>CCR2<\/jats:italic>\n                      -dependent genes involved in immune response and apoptosis, including\n                      <jats:italic>Trim30<\/jats:italic>\n                      ,\n                      <jats:italic>Fas<\/jats:italic>\n                      , and\n                      <jats:italic>PD-1<\/jats:italic>\n                      , which were reversed by\n                      <jats:italic>CCR2<\/jats:italic>\n                      antagonists. At the cellular level, H37Ra upregulated\n                      <jats:italic>MCP-1<\/jats:italic>\n                      expression, promoting M2 polarization.\n                      <jats:italic>MCP-1<\/jats:italic>\n                      Knockdown enhanced macrophage apoptosis, reversed M2 polarization, and suppressed immunosuppressive signaling. Additionally,\n                      <jats:italic>MCP-1<\/jats:italic>\n                      knockdown increased TNF-\u03b1 and IFN-\u03b3 levels, reduced TGF-\u03b2 and IL-10 secretion, and oppositely regulated ESAT-6 and Beclin-1 expression.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion<\/jats:title>\n                    <jats:p>\n                      The\n                      <jats:italic>MCP-1\/CCR2<\/jats:italic>\n                      axis promotes M2-type macrophage polarization, suppresses apoptosis, and enhances immunosuppressive signaling in the context of H37Ra infection. Targeting\n                      <jats:italic>CCR2\/MCP-1<\/jats:italic>\n                      may provide a promising strategy to reverse immune evasion and restore host defense mechanisms during MTB infection.\n                    <\/jats:p>\n                  <\/jats:sec>","DOI":"10.3389\/fimmu.2025.1698369","type":"journal-article","created":{"date-parts":[[2026,1,5]],"date-time":"2026-01-05T07:43:38Z","timestamp":1767599018000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":4,"title":["MCP-1\/CCR2 axis regulates M2 macrophage polarization and immunosuppression in mycobacterium 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