{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,3]],"date-time":"2026-09-03T17:07:05Z","timestamp":1788455225910,"version":"build-2803163510"},"reference-count":63,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2022,9,6]],"date-time":"2022-09-06T00:00:00Z","timestamp":1662422400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100001659","name":"Deutsche Forschungsgemeinschaft","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100001659","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Immunol."],"abstract":"<jats:p>Sepsis is associated with profound immune dysregulation that increases the risk for life-threatening secondary infections: Dendritic cells (DCs) undergo functional reprogramming due to yet unknown changes during differentiation in the bone marrow (BM). In parallel, lymphopenia and exhaustion of T lymphocytes interfere with antigen-specific adaptive immunity. We hypothesized that there exists a link between T cells and the modulation of DC differentiation in the BM during murine polymicrobial sepsis. Sepsis was induced by cecal ligation and puncture (CLP), a model for human bacterial sepsis. At different time points after CLP, the BM and spleen were analyzed in terms of T-cell subpopulations, activation, and Interferon (IFN)-\u03b3 synthesis as well as the number of pre-DCs. BM-derived DCs were generated <jats:italic>in vitro<\/jats:italic>. We observed that na\u00efve and virtual memory CD8<jats:sup>+<\/jats:sup> T cells, but not CD4<jats:sup>+<\/jats:sup> T cells, were activated in an antigen-independent manner and accumulated in the BM early after CLP, whereas lymphopenia was evident in the spleen. The number of pre-DCs strongly declined during acute sepsis in the BM and almost recovered by day 4 after CLP, which required the presence of CD8<jats:sup>+<\/jats:sup> T cells. Adoptive transfer experiments and <jats:italic>in vitro<\/jats:italic> studies with purified T cells revealed that Toll-like receptor 2 (TLR2) signaling in CD8<jats:sup>+<\/jats:sup> T cells suppressed their capacity to secrete IFN-\u03b3 and was sufficient to change the transcriptome of the BM during sepsis. Moreover, the diminished IFN-\u03b3 production of CD8<jats:sup>+<\/jats:sup> T cells favored the differentiation of DCs with increased production of the immune-activating cytokine Interleukin (IL)-12. These data identify a novel role of CD8<jats:sup>+<\/jats:sup> T cells in the BM during sepsis as they sense TLR2 ligands and control the number and function of <jats:italic>de novo<\/jats:italic> differentiating DCs.<\/jats:p>","DOI":"10.3389\/fimmu.2022.945409","type":"journal-article","created":{"date-parts":[[2022,9,6]],"date-time":"2022-09-06T08:13:40Z","timestamp":1662452020000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":14,"title":["TLR2-induced CD8+ T-cell deactivation shapes dendritic cell differentiation in the bone marrow during 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