Abstract
The interactions between dendritic cells (DCs) and other innate immune cells during acute bacterial infection remain poorly understood. To investigate this cross-talk, we generated CD11c-cre-mediated early growth response gene-2 knockout (Egr2cKO) mice and used an acute Listeria monocytogenes (LM) infection model. In wild-type mice, LM infection induced the generation of monocyte-derived DCs (Mo-DCs), which suppressed the conversion of natural killer (NK) cells into immunosuppressive NK cells, while Mo-DC-derived TNF-α enhanced neutrophil (NP) activity to control infection. In contrast, Egr2cKO mice exhibited significantly increased susceptibility to LM infection compared with their Egr2-floxed wild-type littermates, primarily due to a deficiency in Mo-DCs. Instead, monocytes in Egr2cKO mice differentiated predominantly into macrophages, which expressed interleukin-15/interleukin-15R and promoted the expansion of immunosuppressive CD11blowCD27+TIGIT+ NK cells. These NK cells produced TGF-β, thereby suppressing NP-mediated NETosis. In vivo depletion of NK cells in Egr2cKO mice partially restored protective immunity, whereas depletion of NPs further exacerbated susceptibility to LM infection. In conclusion, our study demonstrates that Egr2-dependent Mo-DCs play a pivotal role in host defense against acute LM infection by restraining the expansion of immunoregulatory NK cells and enhancing TNF-α-mediated NPs NETosis. These findings highlight the Mo-DC/NK/NP immune axis as a key element of the innate immune response to acute bacterial infection.