Roles of the MyD88-IRAK pathway and the TRIF-IRF pathway in the host defense against Pseudomonas aeruginosa infection

Lung infection with Pseudomonas aeruginosa is a major cause of death in immune compromised individuals and cystic fibrosis patients. Mechanisms of host defense against this important bacterium are still unclear. Autophagy is derived from Greek roots: auto, meaning 'self', and phagy, 'to eat'. Originally, autophagy is recognized as a catabolic process involving the degradation of a cell's own components for generation of energy, a mechanism for cell survival during nutrient depletion conditions. Recently, the opposite effects of autophagy in pathogen-mediated pathogenesis have been recognized. Some pathogens appear to exploit autophagy mechanism to mediate host cell damage and favor pathogen growth, while other pathogens are eliminated by autophagy mechanism by the host cells. Our recent study showed for the first time that P. aeruginosa also induces autophagy in human and mouse cells. Promotion of autophagy improves the host defense against P. aeruginosa lung infection. The molecular events involved in this process are not known. We will use biochemical and genetic approaches to investigate two signal transduction pathways, namely, MyD88 pathway and TRIF pathway in P. aeruginosa-induced autophagy. These studies will provide novel information relevant to our understanding the mechanisms involved in P. aeruginosa-induced immune response.