Activation of innate immune antiviral responses by Nod2

Ahmed Sabbah, et al. Nature Immunology 10：1073-80 (2009)

Speaker : Huo-Sheng Chiou (邱穫升)                             Time : 15:10~16:00, Dec. 02, 2009

Commentator : Shun-hua Chen, Ph.D. (陳舜華博士)              Place : Room 601

Abstract

Pathogen recognition receptor (PRR) plays an important role in innate immune system during pathogens invasion. By recognizing individual pathogen-associated molecular patterns (PAMP), PRR can lead to interferon secretion or cell apoptosis in order to eliminate these pathogens. Nod-like receptors (NLR), different from toll-like receptor, are cytosolic proteins that usually recognize intercellular PAMP. Previously studies have shown that Nod2, a member of NLR family, can recognize the muramyl dipeptide component of the bacterial cell wall and transmits signals to NF-kB activation pathway for regulating the expression of inflammatory genes. In this paper, the authors have discovered that Nod2 can sense viral ssRNAs, and that the function of Nod2 is associated with type I interferons secretion. In vitro studies show that both synthetic and viral ssRNAs can trigger the activation of Nod2. When Nod2 is activated, it transmits the signal to mitochondrial anti-viral signaling protein which activates interferon regulator 3 (IRF3), then leads to IFN-b production. Also, the mutagenesis assay shows that activated Nod2 interacts with mitochondrial anti-viral signaling protein (MAVS) with its nucleotide-binding domain and carboxyl leucine-rich repeats. Furthermore, in vivo experiments show that Nod2-deficent mice infected with Human respiratory syncytial virus have less IFN-b production and lower survival rate than the wild type. Taken together, this paper introduces a previous unknown function of Nod2 in recognizing ssRNA viruses that plays an essential role in triggering pro-inflammatory response in innate immunity.

References 

1.     Luigi Franchi et al. Function of Nod-like receptors in microbial recognition and host Defense. Immunol. Rev. 227 : 106–128 (2009).

2.     Taro Kawai et al. The roles of TLRs, RLRs and NLRs in pathogen recognition. Int. Immunol. 21:317–337 (2009).