Intestine lamina propria CD4+T cells promote the bactericidal activity of macrophages via galectin-9 and Tim-3 interaction during Salmonella typhimurium infection (MUC5P.760)

Abstract

Abstract The intestinal immune system is crucial for protection the host from pathogenic infection and maintenance of mucosal homeostasis. The intestine lamina propria macrophages are main effector cells in innate resistance to intracellular microbial pathogens. In the present study, we found that Salmonella typhimurium infection augmented the Tim-3 expression on intestinal lamina propria CD4+T cells and enhanced galectin-9 expression on F4/80+CD11c+macrophages. Moreover, CD4+T cells promote the activation and bactericidal activity of F4/80+CD11c+macrophages via galectin-9 and Tim-3 interaction during Salmonella typhimurium infection. Blockade the interaction of Tim-3 and galectin-9 with a-Lactose significantly attenuated the killing of intracellular bacteria by macrophages. Furthermore, the interaction of Tim-3 and galectin-9 also promoted the formation and activation of inflammasome, which leads to the cleavage of caspase-1 and IL-1β. The secretion of active IL-1β further improved bactericidal activity of macrophages and expression of galectin-9 on macrophages. These results demonstrated the critical role of the cross-talk between CD4+T cell and macrophage, in particularly the interaction of Tim-3 and galectin-9, in antimicrobial immunity and control intestinal pathogen infection.