How the noninflammasome NLRs function in the innate immune system.
NLR (nucleotide-binding domain, leucine-rich repeat-containing) proteins have rapidly emerged as central regulators of immunity and inflammation with demonstrated relevance to human diseases. Much attention has focused on the ability of several NLRs to activate the inflammasome complex and drive proteolytic processing of inflammatory cytokines; however, NLRs also regulate important inflammasome-independent functions in the immune system. We discuss several of these functions, including the regulation of canonical and noncanonical NF-kappaB activation, mitogen-activated protein kinase activation, cytokine and chemokine production, antimicrobial reactive oxygen species production, type I interferon production, and ribonuclease L activity. We also explore the mechanistic basis of these functions and describe current challenges in the field.
Ting
Jenny P Y
JP
Department of Microbiology-Immunology, University of North Carolina, Chapel Hill, NC 27599, USA. jpyting@med.unc.edu
Duncan
Joseph A
JA
Lei
Yu
Y
D000818:Animals; D016207:Cytokines / Q000378:metabolism; D004722:Endoribonucleases / Q000378:metabolism; D006801:Humans; D007113:Immunity, Innate; D007249:Inflammation; D007370:Interferon Type I / Q000378:metabolism; D047908:Intracellular Signaling Peptides and Proteins / Q000737:chemistry / Q000378:metabolism*; D024101:Mitochondrial Proteins / Q000378:metabolism; D020928:Mitogen-Activated Protein Kinases / Q000378:metabolism; D016328:NF-kappa B / Q000378:metabolism; D053474:Nod1 Signaling Adaptor Protein / Q000378:metabolism; D053473:Nod2 Signaling Adaptor Protein / Q000378:metabolism; D054730:Protein Interaction Domains and Motifs; D051192:Receptors, Pattern Recognition / Q000737:chemistry / Q000378:metabolism*; D015398:Signal Transduction
D016207:Cytokines; D007370:Interferon Type I; D047908:Intracellular Signaling Peptides and Proteins; D024101:Mitochondrial Proteins; D016328:NF-kappa B; D053474:Nod1 Signaling Adaptor Protein; D053473:Nod2 Signaling Adaptor Protein; D051192:Receptors, Pattern Recognition; D020928:Mitogen-Activated Protein Kinases; D004722:Endoribonucleases; C031956:2-5A-dependent ribonuclease