Abstract
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 Chlamydia muridarum infection. Transcriptomic analyses revealed significant downregulation of key genes in DCs from NK-depleted mice involved in type I immunity, including IL12rb2, IL-18rap, and chemokine signaling components such as Ccl3, Ccl5, and Ccr5. 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.