Inflammasomes complexes in anti-microbial immunity

The innate immune system provides the first line of defense against infections by rapidly recognizing and eliminating invading microbes. An important component of innate immunity are pattern recognition receptors, which are sensors that constantly monitor the extracellular and intracellular space of host cells for molecules of bacterial origin. Once the presence of bacteria is detected, these sensors initiate an inflammatory response. A subset of these pattern recognition receptors initiates the assembly of cytosolic multi-protein complexes called inflammasomes. The inflammasome complex is a large filamentous assembly formed by progressive oligomerization of receptors and adaptor proteins and serves as an activation platform for inflammatory caspases, a group of cysteine proteases. The prototypic caspase activated by canonical inflammasomes in caspase-1, which control the release of cytokines like IL-1b. Uncontrolled activation of the inflammasome by gain-of-function mutations or sterile inflammatory triggers is an underlying cause of many (auto-) inflammatory diseases. By characterizing new players and regulatory mechanism that control complex assembly and downstream signaling, we aim at identifying new targets for therapeutic modulation of inflammasome activity.