NLR Proteins

Muñoz-Wolf, Natalia, Lavelle, Ed C, Natalia Muñoz-Wolf, Ed C. Lavelle

Francesco Di Virgilio, Pablo Pelegrín

For many years innate immunity was regarded as a relatively nonspecific set of mechanisms serving as a first line of defence to contain infections while the more refined adaptive immune response was developing. The discovery of pattern recognition receptors (PRRs) revolutionised the prevailing view of innate immunity, revealing its intimate connection with adaptive immunity and generation of effector and memory T- and B-cell responses. Among the PRRs, families of Toll-like receptors (TLRs), C-type lectin receptors (CLR), retinoic acid-inducible gene-I (RIG-I)-like receptors (RLRs) and nucleotide-binding domain, leucine-rich repeat-containing protein receptors (NLRs), along with a number of cytosolic DNA sensors and the family of absent in melanoma (AIM)-like receptors (ALRs), have been characterised. NLR sensors have been a particular focus of attention, and some NLRs have emerged as key orchestrators of the inflammatory response through the formation of large multiprotein complexes termed inflammasomes. However, several other functions not related to inflammasomes have also been described for NLRs. This chapter introduces the different families of PRRs, their signalling pathways, cross-regulation and their roles in immunosurveillance. The structure and function of NLRs is also discussed with particular focus on the non-inflammasome NLRs.