{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,23]],"date-time":"2026-07-23T11:14:56Z","timestamp":1784805296753,"version":"3.55.0"},"reference-count":38,"publisher":"Public Library of Science (PLoS)","issue":"2","license":[{"start":{"date-parts":[[2025,2,4]],"date-time":"2025-02-04T00:00:00Z","timestamp":1738627200000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["31870889"],"award-info":[{"award-number":["31870889"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["31070797"],"award-info":[{"award-number":["31070797"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]},{"name":"The Key Program of Tianjin Science and Technology Commission","award":["19JCZDJC35800"],"award-info":[{"award-number":["19JCZDJC35800"]}]},{"name":"The Key Program of Tianjin Science and Technology Commission","award":["15JCZDJC34900"],"award-info":[{"award-number":["15JCZDJC34900"]}]}],"content-domain":{"domain":["www.plospathogens.org"],"crossmark-restriction":false},"short-container-title":["PLoS Pathog"],"abstract":"<jats:p>CCR2, a member of the G protein-coupled receptor (GPCR) superfamily, is widely expressed on monocytes, macrophages, activated T cells, and other cell types, and plays a critical role in coordinating the immune response to various infections. Here we demonstrate that CCR2 expression is significantly elevated during Chlamydia muridarum (<jats:italic>C<\/jats:italic>. <jats:italic>muridarum<\/jats:italic>) respiratory infection, and its absence leads to exacerbated susceptibility, as evidenced by significant weight loss, higher bacterial loads, severe lung pathology, and elevated levels of inflammatory cytokines (<jats:italic>il-1\u03b2<\/jats:italic>, <jats:italic>tnf\u03b1<\/jats:italic>, and <jats:italic>il-6<\/jats:italic>). The absence of <jats:italic>ccr2<\/jats:italic> impairs both myeloid cell infiltration and T cell responses, which are crucial for effective immune defense. Specifically, <jats:italic>ccr2<\/jats:italic> deficiency disrupts the differentiation and response of Th1 cells, which are the primary effector lineage responsible for clearing chlamydia through secretion of interferon-gamma (IFN-\u03b3). As a result, there is a significant decrease in CD3<jats:sup>+<\/jats:sup>CD4<jats:sup>+<\/jats:sup>IFN-\u03b3<jats:sup>+<\/jats:sup> T cells in the lung and spleen, accompanied by reduced levels of IFN-\u03b3 protein and mRNA, as well as downregulated mRNA expression of Th1-promoting cytokines (<jats:italic>il-12p35<\/jats:italic>, <jats:italic>il-12p40<\/jats:italic>) and transcription factors (<jats:italic>stat4<\/jats:italic>, <jats:italic>T-bet<\/jats:italic>), which play crucial roles in Th1 differentiation. Moreover, <jats:italic>ccr2<\/jats:italic> deficiency greatly diminishes STAT1 phosphorylation, a key regulator of IFN-\u03b3 secretion by Th1 cells. Meanwhile, we also observed a significant reduction in IFN-\u03b3 secretion by CD8<jats:sup>+<\/jats:sup> T cells following <jats:italic>ccr2<\/jats:italic> deficiency. Conversely, <jats:italic>ccr2<\/jats:italic><jats:sup>-\/-<\/jats:sup> mice exhibit an exaggerated Th2-type immune response, with elevated levels of Th2-promoting cytokines (IL-4), transcription factors (STAT6 and <jats:italic>gata3<\/jats:italic>), and <jats:italic>il-5<\/jats:italic>, which together lead to more severe lung tissue damage and increased susceptibility to infection. Furthermore, these mice show higher levels of IL-17 along with an enhanced Th17-type immune response, characterized by increased Th17-promoting cytokines <jats:italic>TGFB<\/jats:italic>, transcription factors <jats:italic>stat3<\/jats:italic> and <jats:italic>ROR\u03b3t<\/jats:italic>, and <jats:italic>il-21<\/jats:italic>, suggesting a compensatory mechanism that drives neutrophil infiltration to exacerbate lung inflammation. These findings underscore the pivotal role of CCR2, a chemokine receptor, in orchestrating the immune response to Chlamydia infection by facilitating Th1 cells differentiation while restraining Th2-type and Th17-type immune responses, thereby alleviating pulmonary inflammation.<\/jats:p>","DOI":"10.1371\/journal.ppat.1012912","type":"journal-article","created":{"date-parts":[[2025,2,4]],"date-time":"2025-02-04T18:21:24Z","timestamp":1738693284000},"page":"e1012912","update-policy":"https:\/\/doi.org\/10.1371\/journal.ppat.corrections_policy","source":"Crossref","is-referenced-by-count":12,"title":["CCR2 signaling regulates anti-chlamydia T cell immune responses in the 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