Nod1 is a member of family of intracellular proteins that mediate host recognition of bacterial peptidoglycan. To characterize immune responses mediated by Nod1, synthetic ligand compounds possessing enhanced ability to stimulate Nod1 were developed to study the function of Nod1. Stimulation of epithelial cells with Nod1 stimulatory molecules induced chemokines and other proinflammatory molecules that are important for innate immune responses and recruitment of acute inflammatory cells. Administration of Nod1 ligands into mice induced chemokines and recruitment of acute inflammatory cells, an activity that was abolished in Nod1-null mice. Microarray analysis revealed that Nod1 stimulation induces a restricted number of genes in intestinal epithelial cells compared with that induced by tumor necrosis factor (TNF) α. Nod1 stimulation did not induce TNFα, interleukin 12, and interferon γ, suggesting that the primary role of Nod1 is to induce the recruitment of immune cells. These results indicate that Nod1 functions as a pathogen recognition molecule to induce expression of molecules involved in the early stages of the innate immune response.
Nod1 acts as an intracellular receptor to stimulate chemokine production and neutrophil recruitment in vivo
Abbreviations used: AcAiQ, d-Ala-Gln-octadecyl ester; AcMTP, MurNAc-l-Ala-γ-d-Glu-l-Lys(stearoyl)-OH; DAP, diaminopimelic acid; GlcNAc, N-acetyl-glucosamyl; HEK, human embryonic kidney; iE-DAP, γ-d-glutamyl-meso-DAP; iQ-DAP, γ-d-glutaminyl-meso-DAP; MurNAc, N-acetyl-muramyl; PGN, peptidoglycan; TLR, Toll-like receptor.
J. Masumoto and K. Yang contributed equally to this work.
J. Masumoto's present address is Dept. of Laboratory Medicine, Shinshu University Hospital, Nagano 390-8621, Japan.
Y. Horie's current address is First Dept. of Internal Medicine, Akita University School of Medicine, Akita 010-8543, Japan.
Junya Masumoto, Kangkang Yang, Sooryanarayana Varambally, Mizuho Hasegawa, Scott A. Tomlins, Su Qiu, Yukari Fujimoto, Akiko Kawasaki, Simon J. Foster, Yasuo Horie, Tak W. Mak, Gabriel Núñez, Arul M. Chinnaiyan, Koichi Fukase, Naohiro Inohara; Nod1 acts as an intracellular receptor to stimulate chemokine production and neutrophil recruitment in vivo . J Exp Med 23 January 2006; 203 (1): 203–213. doi: https://doi.org/10.1084/jem.20051229
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