1050 Neutrophil-intrinsic NLRP12 and caspase-8 signal for inflammasome-mediated host defense against staphylococcus aureus skin infections

Staphylococcus aureus is the leading cause of skin and soft tissue infections. With emergence antibiotic-resistant bacteria, there an unmet clinical need to develop novel therapies treat The inflammasome components involved in response S. stimulation are well established vitro immune cell cultures. However, formation cells during vivo infections not entirely understood. Therefore, we used mouse model intradermal infection first define with Using ASC-Citrine reporter mouse, observed neutrophils as predominant inflammasome-forming population infected skin. To elucidate inflammasome-associated nod-like receptor, NLRP3, AIM2, or NLRC4-deficient mice, but unexpectedly found no host defense defect compared WT mice. by performing co-immunoprecipitations from biopsies, discovered that sensor, NLRP12, associated ASC adaptor protein. Next, set out identify caspases infecting caspase-1, -11, caspase-1/11 double-deficient mice significant difference Thus, generated S100A8Cre-Casp8fl/fl (neutrophil-specific deletion caspase-8) a Collectively, our data indicated NLRP12 caspase-8 signaling was critical for protection against infections, providing potential therapeutic targets.