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Nucleotide-Binding Oligomerization Domain-Like Receptors: Intracellular Pattern Recognition Molecules for Pathogen Detection and Host Defense¹

Department of Pathology and Comprehensive Cancer Center, University of Michigan Medical School, Ann Arbor, MI 48109

The nucleotide binding oligomerization domain-like receptor (NLR) family of pattern recognition molecules is involved in a diverse array of processes required for host immune responses against invading pathogens. Unlike TLRs that mediate extracellular recognition of microbes, several NLRs sense pathogens in the cytosol and upon activation induce host defense signaling pathways. Although TLRs and NLRs differ in their mode of pathogen recognition and function, they share similar domains for microbial sensing and cooperate to elicit immune responses against the pathogen. Genetic variation in several NLR genes is associated with the development of inflammatory disorders or increased susceptibility to microbial infection. Further understanding of NLRs should provide critical insight into the mechanisms of host defense and the pathogenesis of inflammatory diseases.

The costs of publication of this article were defrayed in part by the payment of page charges. This article must therefore be hereby marked advertisement in accordance with 18 U.S.C. Section 1734 solely to indicate this fact.

¹ This work was supported by National Institutes of Health Grants AI063331, AI064748, DK61707, and DK067628 and a grant from the Eli and Edythe L. Broad Foundation (to G. N.). Other support includes a fellowship from Fondazione Italiana Ricerca sul Cancro (to L.F.), a Career Development Award from the Crohn’s and Colitis Foundation of America (to C.M.), and Grant T32/HL007517 from the National Institutes of Health (T.-D.K.).

² Address correspondence and reprint requests to Dr. Gabriel Núñez, Department of Pathology and Comprehensive Cancer Center, University of Michigan Medical School, 1500 East Medical Center Drive, Ann Arbor, MI 48109. E-mail address: bclx{at}umich.edu

³ Abbreviations used in this paper: PAMP, pathogen-associated molecular pattern; Nod, nucleotide-binding oligomerization domain; CARD, caspase-recruitment domain; LRR, leucine-rich repeat; ASC, apoptosis-associated speck-like protein containing a CARD; MDP, muramyl dipeptide; NLR, Nod-like receptor; PGN, peptidoglycan; DAP, diaminopimelic acid; iE-DAP, -D-glutamyl-meso-DAP; IKK, IB kinase; CD, Crohn’s disease; BS, Blau syndrome; FCAS, familial cold autoinflammatory syndrome.

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