Listeria monocytogenes에 대한 선천 면역반응에서 DRG2의 역할 연구

Abstract

The ability of macrophages to produce inflammatory cytokines plays a pivotal role in the innate immune response. Here we demonstrated that developmentally regulated GTP binding protein 2 (DRG2) −/− macrophages are intrinsically defective in migration and inflammatory cytokine production. DRG2-/- macrophages showed increased inhibitory phosphorylation of GSK3β and decreased transcriptional activity of NF-κB upon infection with Listeria monocytogenes. L. monocytogenes is a pathogen causing listeriosis that can be serious for individuals with impaired immune system. The innate immune response is critical for the control of early L. monocytogenes infection. Here, we report that DRG2 is a major regulator of innate immune response against L. monocytogenes infection. Using a DRG2−/− mouse, we determined that DRG2 deficiency decreased survival upon L. monocytogenes infection. Additionally, in DRG2 macrophage specific KO mice, compared to DRG2 fl/fl mice, decreased survival upon L. monocytogenes infection. Lastly, DRG2−/− macrophages showed increase in the inhibitory phosphorylation of GSK3β and decrease in the transcriptional activity of NF-κB upon L. monocytogenes infection. Our findings reveal a novel function of DRG2 in the cytokine production of immune cells and control of L. monocytogenes infection and host resistance.