{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,7,30]],"date-time":"2025-07-30T09:55:24Z","timestamp":1753869324372,"version":"3.41.2"},"reference-count":28,"publisher":"Wiley","issue":"12","license":[{"start":{"date-parts":[[2024,12,18]],"date-time":"2024-12-18T00:00:00Z","timestamp":1734480000000},"content-version":"vor","delay-in-days":17,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Immunity Inflam &amp;amp; Disease"],"published-print":{"date-parts":[[2024,12]]},"abstract":"<jats:title>ABSTRACT<\/jats:title><jats:sec><jats:title>Objective<\/jats:title><jats:p>To elucidate the role of phosphatidylcholine\u2010specific phospholipase C (PC\u2010PLC) in the antituberculosis (anti\u2010TB) immune response mediated by dendritic cells (DCs).<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>In vivo, C57BL\/6J mice infected with the <jats:italic>Mycobacterium tuberculosis<\/jats:italic> strain H37Rv. Before infection, the mice were pretreated with the PC\u2010PLC inhibitor D609. Bacillary loads in lung and spleen tissues were quantified through colony\u2010forming unit (CFU) assays. Hematoxylin and eosin (H&amp;E) staining was performed to assess inflammatory infiltration and tissue damage. Levels of inflammatory mediators in peripheral venous blood were quantified using enzyme\u2010linked immunosorbent assays (ELISAs). Flow cytometry was employed to determine the proportions of conventional DCs (cDCs) and their subsets, cDC1 and cDC2, within lung, spleen, and lymph node tissues. In vitro, mouse bone marrow\u2010derived dendritic cells (BMDCs) pretreated with D609. The expression levels of chemokines and pro\u2010inflammatory cytokines were assessed via quantitative polymerase chain reaction (qPCR) and ELISA. BMDCs were loaded with H37Rv expressing red fluorescent protein (RFP\u2010H37Rv) or DQ\u2010OVA, and flow cytometry was utilized to analyze the impact of D609 on antigen phagocytosis and processing. Furthermore, flow cytometry was employed to evaluate the effect of D609 pretreatment on the expression levels of costimulatory molecules on BMDCs. The capacity of D609\u2010treated BMDCs to activate and proliferate T cells, as well as to induce interferon\u2010gamma (IFN\u2010\u03b3) secretion, was assessed through a DC\u2010T cell coculture system.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>In vivo analysis revealed that mice pretreated with D609 exhibited a marked increase in tissue bacterial load, enhanced inflammatory infiltration, and a reduction in pro\u2010inflammatory mediator expression in peripheral venous blood. There was a notable decrease in the number of cDCs in lung and lymph node tissues, with a pronounced reduction in cDC1 in the lungs and cDC2 in the lymph nodes. In vitro studies demonstrated that D609 pretreated BMDCs displayed a significant decline in inflammatory mediator production, antigen phagocytosis, and antigen processing capabilities, potentially due to altered expression of costimulatory molecules. Coculture experiments indicated that D609 pretreated BMDCs showed a substantial reduction in their ability to stimulate T cell activation, proliferation, and IFN\u2010\u03b3 secretion.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusion<\/jats:title><jats:p>Our findings suggest that PC\u2010PLC plays a critical role in the functionality of DCs, including the production of chemokines and pro\u2010inflammatory cytokines, migration to lymph nodes, and antigen presentation to T cells, which collectively contribute to T cell activation and effective clearance of Mycobacterium tuberculosis. Further investigation into the regulatory mechanisms of PC\u2010PLC in DCs may uncover novel therapeutic targets for the development of advanced anti\u2010TB treatments.<\/jats:p><\/jats:sec>","DOI":"10.1002\/iid3.70103","type":"journal-article","created":{"date-parts":[[2024,12,18]],"date-time":"2024-12-18T15:40:26Z","timestamp":1734536426000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["D609 Suppresses Antituberculosis Response by Regulating Dendritic Cells Antigen Presentation"],"prefix":"10.1002","volume":"12","author":[{"given":"Honglin","family":"Liu","sequence":"first","affiliation":[{"name":"Department of Clinical Laboratory Zhongshan Second People's Hospital Zhongshan Guangdong China"},{"name":"Institute of Molecular Immunology, School of Laboratory Medicine and Biotechnology, Southern Medical University Guangzhou Guangdong 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