NOD so fast: NLRX1 puts the brake on inflammation

Abstract

In this issue of Immunity, Allen et al. (2011) and Xia et al. (2011) provide in vivo and biochemical evidence that NLRX1, a member of the nucleotide binding domain and leucine-rich-repeat-containing protein family, functions as a negative regulator of RIG-I and Toll-like receptors.

Figure 1. NLRX1 Blocks RIG-I and NF-κB Signaling

Upon detection of viral- or bacterial-derived PAMPs, RIG-I and TLR4 facilitate the production of antiviral and/or proinflammatory cytokines via IRF3 and NF-κB, respectively. In RIG-I signaling, NLRX1 targets the MAVS adaptor to terminate downstream signal transmission to the IRF3 and NF-κB transcription factors. Alternatively, in TLR4 signaling pathways, NLRX1 undergoes ligand-dependent Lys63 polyubiquitination and translocation from TRAF6 to the IKK complex, blocking its kinase function and consequently NF-κB activation.