Wang Xinting, Zhang Chunyan, Zhang Yongci, Wang Shuhe, Thomas Rony, Yang Xi
Department of Immunology, University of Manitoba, Winnipeg, MB R3E 0T5, Canada.
Department of Biochemistry and Molecular Biology, Department of Immunology, School of Basic Medical Science, Tianjin Medical University, Tianjin 300070, China.
Int J Mol Sci. 2025 Apr 16;26(8):3769. doi: 10.3390/ijms26083769.
Previous studies have demonstrated the significant impact of NK cells on adaptive immune responses against chlamydial infections through modulating DCs, yet the molecular mechanisms remain incompletely understood. This study investigates the role of NK cells in modulating DC signaling pathways and the recruitment of DCs during infection. Transcriptomic analyses revealed significant downregulation of key genes in DCs from NK-depleted mice involved in type I immunity, including , and chemokine signaling components such as , , and Gene ontology (GO) analyses confirmed impaired chemokine-chemokine receptor interactions in DCs from NK-depleted mice. Moreover, flow cytometry analysis showed that NK-cell depletion reduced CCR5 expression on splenic and pulmonary DCs, impairing their migration toward CCL3 and CCL5. Furthermore, IFN-γ enhanced CCR5 expression on the surface of DCs, consequently promoting their migration, which was blocked by anti-IFN-γ antibodies. In vitro migration assays showed that treatment of DCs with IFN-γ increased their responsiveness to CCL3 and CCL5, the ligands of CCR5. Collectively, this study provides new insights into the indispensable role of NK cells in orchestrating DC signaling and the recruitment of DCs during chlamydial infection.
先前的研究表明，自然杀伤细胞（NK细胞）通过调节树突状细胞（DCs），对衣原体感染的适应性免疫反应具有显著影响，但其分子机制仍未完全明确。本研究调查了NK细胞在调节DC信号通路以及感染期间DC募集过程中的作用。转录组分析显示，来自NK细胞耗竭小鼠的DC中，参与I型免疫的关键基因显著下调，包括 ，以及趋化因子信号成分，如 、 和 。基因本体（GO）分析证实，NK细胞耗竭小鼠的DC中趋化因子 - 趋化因子受体相互作用受损。此外，流式细胞术分析表明，NK细胞耗竭降低了脾脏和肺部DC上CCR5的表达，损害了它们向CCL3和CCL5的迁移。此外，干扰素 - γ（IFN - γ）增强了DC表面CCR5的表达，从而促进了它们的迁移，而抗IFN - γ抗体可阻断这一过程。体外迁移试验表明，用IFN - γ处理DC可增加其对CCR5配体CCL3和CCL5的反应性。总的来说，本研究为NK细胞在衣原体感染期间协调DC信号传导和DC募集方面的不可或缺作用提供了新的见解。
