Characterizing the function of a novel immune sensor NLRP1 in skin infection and inflammation

Bacterial infection of the skin represents a significant clinical problem in Southeast Asia and world-wide, particularly those caused by antibiotic resistant bacterial strains such as methicillin-resistant Staphylococcus aureus (MRSA). We have recently identified Nod-like Receptor Protein-1, NLRP1 as an orphan inflammasome protein specifically involved in skin immunity. Here we propose that wild-type NLRP1 is a bona fide sensor for Gram positive bacteria including MRSA. We aim to identify the cognate ligand molecule recognized by NLRP1 and determine its function in inflammasome signaling and S. aureus infection. This work will lead to better understanding of a fundamental question in innate immunity, i.e. how human cells sense pathogens, and provide new opportunities to develop better treatment for persistent bacterial skin infections. Aim 1 will determine the role of NLRP1 in inflammasome activation during Staphylococcus aureus skin infection.Aim 2 will identify the cognate NLRP1 ligand and determine its function in inflammasome activation.