Role Of SRC-3 In Listeria Monocytogenes Infection

Steroid receptor coactivator 3(SRC-3)is a transcriptional coactivator which interacts with nuclear receptors and other transcription factors to enhance their effects on targetgene transcription.Previously,we reported that in E.coil-induced septic peritonitis,SRC-3 in macrophage can inhibit the cell apoptosis and cytokines production,and enhance in bacterial clearance,which highlights a pivotal role of SRC-3 in the host defense system against bacterial infection.In C.rodentium infection,SRC-3 can promote the CXCL2 transcription through activating NF-κB signaling,suggesting that SRC-3 may be involved in host defense against bacterial infection.To investigate the role of SRC-3 in L.monocytogenes infection,we infected the wide-type and SRC-3-/-mice through tail vein.We found SRC-3-/-mice exhibited increased survival percent and enhanced clearance of L.monocytogenes,suggesting SRC-3 deficiency decreased sensibility to L.monocytogenes.Besides,SRC-3 can decrease the ROS production through regulating NRROS expression in RAW264.7 cells and BMDM.In addition,there were less apoptosis-related genes and T cell apoptosis after infection with L.monocytogenes compared to wide-type mice in SRC-3-/-mice.Interestingly,the proinflammatory cytokines level in SRC-3-/-mice is decreased compared to wide-type.And the ISR-related genes mRNA level also decreased in the spleen of SRC-3-/-mice.Finally,we test the IFN-p promoter activity in RAW264.7 and foud SRC-3 can promote its activity.Howver when mutate the IRF-E,its activity was decreased.Therefore,SRC-3 may protect the host from defending against L.monocytogenes infection through upregulating NRROS expression and splenocyte apoptosis.On the other hand,SRC-3 may regulate the proinflammatory level through type-I IFN.