Abstract

Inflammation is an essential host response to infection and injury. At the heart of inflammation research is an attempt to understand the regulation of the pro-inflammatory cytokine interleukin-1β (IL-1β), which is central to host responses to infection, but also causes tissue injury when activated inappropriately. IL-1β is produced by many cell types as an inactive precursor (pro-IL-1β) and requires processing by the protease caspase-1 to obtain full biological activity. Caspase-1 is also produced as a precursor and becomes activated following recruitment to an intracellular multi-molecular scaffold called an inflammasome. Multiple inflammasomes are described, each defined by the presence of a cytosolic pattern recognition receptor (PRR). The PRR NLRP3 forms an inflammasome that drives the inflammatory response to pathogens such as Staphylococcus aureus or Listeria monocytogenes, but is also known to drive damaging inflammation during sterile inflammatory insults. The goal of my research is to understand the mechanisms regulating the production of IL-1 and how they contribute to disease.