Project 170521

Macrophages are key immune cells for detecting and eliminating microbial pathogens. Many pathogens induce macrophage death as a virulence tactic to survive and disseminate within the host. Recent studies have identified a family of intracellular receptors known as the nucleotide-binding domain and leucine-rich repeats(NLRs) which recognize intracellular microbial components. Activation of these receptors in macrophages induces rapid release of key inflammatory cytokines and macrophage cell death. Production of cytokines induces inflammation and is important for limiting microbial infections. However, rapid cell death can cause the spillage of unnecessary inflammatory mediators, resulting in overwhelming local inflammation and tissue damages, and defects in immune system by depleting macrophages. However, detailed mechanisms regarding the process of cytokine release and cell death remains to be investigated. This study is to investigate detailed signaling and molecular mechanisms of cytokine release and cell death, and examine the contribution of macrophage death during bacterial infections. This study will provide valuable and fundamental information on interactions between microbes and the host cells, and provide information on designing novel therapeutic tools for treating various bacterial and viral infections.