Molecular characterization of a novel mitochondrial Nod-like receptor X1 in chicken that negatively regulates IFN-ꞵ expression via STING

Nod-like receptor X1 (NLRX1) is known for its unique mitochondrial localization and plays a negative role in innate immunity. The initial characterization and function of chicken NLRX1 remain unclear. Here, chicken mitochondrial-targeted NLRX1 (chNLRX1) protein was identified. It had relatively conserved domains, a unique N-terminal “X” mitochondrial-targeting domain (MT) and two highly conserved motifs at positions 510–520 and 412– 421. Furthermore, chNLRX1 had a unique 53aa N-terminus-MT consistent with its localization to mitochondria. Additionally, chNLRX1 was observed to reduce the DNA sensing adaptor stimulator of interferon genes (STING)-induced IFN-β by attenuating the STING-TANK-binding kinase 1 (TBK1) interaction, which is a requisite for the STING-TBK1-IFN-β signaling pathway. These results suggested that chNLRX1 negatively regulated type-I interferon production via STING in host innate immunity.