Our work on autophagy involves determining the molecular pathways regulating autophagy during pathogen infection. Autophagy has been recently shown to be an important component of the innate immune response by degrading foreign microbial invaders. The upstream signaling pathways leading to activation of autophagy are not known and currently under investigation in our laboratory.
Our recent study links autophagy to innate immunity toll-like receptor 4 (TLR4). Further, it defines the signaling pathway downstream from TLR4 via TRIF/RIP1/p38MAPK. This pathway maintains cell survival in the context of autophagy associated with infection and is distinct from autophagic cell death. The potential therapeutic use of modulating this pathway is significant. As a proof of concept, we used LPS treatment to force mycobacterium tuberculosis to the autophagosomes and to be lysed by the lysosomes.
