NLRP9 in innate immunity and inflammation.

The nucleotide-binding domain leucine-rich repeat containing receptors (NLRs) are a family of evolutionarily conserved proteins. Several members of NLRs, notably NLRP1, NLRP3 and NLRC4, are able to form cytosolic oligomeric signalling platforms termed inflammasomes to mediate immune response towards pathogens, damage and stress. However, the functions of many NLRs still remain elusive. In the past few years, a couple of less-characterized NLR members are emerging as important signalling molecules with fundamental functions in host defence and inflammation. Among them, NLRP9 is an NLR originally proposed to be expressed and function solely in the reproductive system. Recent evidence has suggested that NLRP9 is also capable of initiating inflammasome formation in the intestine to restrict replication and damage brought by rotavirus infection. Here, we highlight the latest progress in characterization of the role of NLRP9 in infectious and inflammatory diseases, as well as the newest crystallographic and biochemical studies on NLRP9. Finally, we discuss some important questions remained to be answered regarding the molecular and cellular mechanisms governing NLRP9's function in innate immunity and inflammation.