Background

Innate immune cells recognize pathogens through a set of pattern recognition receptors (PRR), which bind to evolutionarily conserved structures on the pathogen surfaces or through ligation of other danger-associated molecular patterns. One family of these receptors are the NOD-like receptors (NLR), which react to the intracellular presence of invading pathogens and/or intracellular danger signals (Meylan et al., 2006). Several PRR, including some NLRs are capable of inducing the formation of so-called inflammasome complexes, which mediate the proteolytic activation of pro-IL-1β, pro-IL-18, and other IL-1 family cytokines (Martinon et al., 2002). Due to the potent pro-inflammatory nature of IL-1β and IL-18, inflammasome activation is a highly regulated, two-step process, involving limited transcription of pro-IL-1β/pro-IL-18, and highly regulated activation of inflammasome receptors (Martinon et al., 2009). NLRP3, one of the most studied inflammasome receptors, responds to a great variety of intracellular danger-associated molecular patterns, including bacterial cell wall components (Martinon et al., 2004), damaged mitochondria (Zhou et al., 2011), and particulate materials (Martinon et al., 2006). Due to their particulate structure, mono sodium urate (MSU) crystals are very potent NLRP3 activators (Martinon et al., 2006), which are widely used for in vitro studies of NLRP3 activation.

In addition to its use for in vitro experiments, MSU can also be used to study the in vivo relevance of inflammasome activation. Here, we described an MSU-induced peritonitis model to easily and quickly study the in vivo relevance and extent NLRP3-inflammasome activation, e.g., upon genetic deletion of proteins that are involved in NLRP3 activation (Chen et al., 2006, Spalinger et al., 2016). In the MSU-induced peritonitis, the first wave of infiltrating immune cells consists mainly of neutrophils, and in the early phase of peritonitis, the number of infiltrating neutrophils correlates with the extent of inflammasome activation and with the production of mature IL-1β (Chen et al., 2006; Spalinger et al., 2016).