NLRs: Nucleotide-Binding Domain and Leucine-Rich-Repeat-Containing Proteins

Eukaryotes have evolved strategies to detect microbial intrusion and instruct immune responses to limit damage from infection. Recognition of microbes and cellular damage relies on the detection of microbe-associated molecular patterns (MAMPs, also called PAMPS, or pathogen-associated molecular patterns) and so-called "danger signals" by various families of host pattern recognition receptors (PRRs). Members of the recently identified protein family of nucleotide-binding domain andleucine-rich-repeat-containing proteins (NLR), including Nod1, Nod2, NLRP3, and NLRC4, have been shown to detect specific microbial motifs and danger signals for regulating host inflammatory responses. Moreover, with the discovery that polymorphisms in NOD1, NOD2, NLRP1, and NLRP3 are associated with susceptibility to chronic inflammatory disorders, the view has emerged that NLRs act not only as sensors butalso can serve as signaling platforms for instructing and balancing host immune responses. In this chapter, we explore the functions of these intracellular innate immune receptors and examine their implication in inflammatory diseases.