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

Aiyun Xu; Xiang Zhu; Tao Song; Zhenyuan Zhang; Fei Fei; Qingxiao Zhu; Xinyue Chang; Hongmei Liu; Fangfang Chen; Fazhi Xu; Lin Li; Xuelan Liu

doi:10.1016/j.psj.2023.103077

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

Poult Sci. 2023 Nov;102(11):103077. doi: 10.1016/j.psj.2023.103077. Epub 2023 Sep 2.

Authors

Aiyun Xu¹, Xiang Zhu², Tao Song¹, Zhenyuan Zhang¹, Fei Fei¹, Qingxiao Zhu¹, Xinyue Chang³, Hongmei Liu⁴, Fangfang Chen⁴, Fazhi Xu⁴, Lin Li⁵, Xuelan Liu⁶

Affiliations

¹ Anhui Province Key Lab of Veterinary Pathobiology and Disease Control, College of Animal Science and Technology, Anhui Agricultural University, Hefei 230036, China; International Immunology Center, Anhui Agricultural University, Hefei 230036, China.
² Agricultural Comprehensive Administrative Law Enforcement Brigade, Mingguang 239400, China.
³ International Immunology Center, Anhui Agricultural University, Hefei 230036, China.
⁴ Anhui Province Key Lab of Veterinary Pathobiology and Disease Control, College of Animal Science and Technology, Anhui Agricultural University, Hefei 230036, China.
⁵ Animal-derived Food Safety Innovation Team, College of Animal Science and Technology, Anhui Agricultural University, Hefei 230036, China.
⁶ Anhui Province Key Lab of Veterinary Pathobiology and Disease Control, College of Animal Science and Technology, Anhui Agricultural University, Hefei 230036, China; International Immunology Center, Anhui Agricultural University, Hefei 230036, China. Electronic address: liuxuelan203@163.com.

Abstract

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 2 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.

Keywords: IFN-β; NLRX1; chicken; mitochondrial localization; negative regulation.