Guangdong Laboratory for Lingnan Modern Agriculture, College of Veterinary Medicine, South China Agricultural University, Guangzhou, China.
Key Laboratory of Animal Vaccine Development, Ministry of Agriculture and Rural Affairs, Guangzhou, China.
Front Immunol. 2023 Jan 6;13:1016214. doi: 10.3389/fimmu.2022.1016214. eCollection 2022.
The innate immune response is a host defense mechanism that induces type I interferon and proinflammatory cytokines. Tripartite motif (TRIM) family proteins have recently emerged as pivotal regulators of type I interferon production in mammals. Here, we first identified duck TRIM29, which encodes 571 amino acids and shows high sequence homology with other bird TRIM29 proteins. DuTRIM29 inhibited IFN-β and IRF7 promoter activation in a dose-dependent manner and downregulated the mRNA expression of IFN-β, IRF7, Mx and IL-6 mediated by duRIG-I. Moreover, duTRIM29 interacted and colocalized with duMAVS in the cytoplasm. DuTRIM29 interacted with duMAVS its C-terminal domains. In addition, duTRIM29 inhibited IFN-β and IRF7 promoter activation and significantly downregulated IFN-β and immune-related gene expression mediated by duMAVS in ducks. Furthermore, duTRIM29 induced K29-linked polyubiquitination and degradation of duMAVS to suppress the expression of IFN-β. Overall, our results demonstrate that duTRIM29 negatively regulates type I IFN production by targeting duMAVS in ducks. This study will contribute to a better understanding of the molecular mechanism regulating the innate immune response by TRIM proteins in ducks.
先天免疫反应是一种宿主防御机制,可诱导 I 型干扰素和促炎细胞因子的产生。三结构域(TRIM)家族蛋白最近已成为哺乳动物 I 型干扰素产生的关键调节因子。在这里,我们首次鉴定了鸭 TRIM29,它编码 571 个氨基酸,与其他鸟类 TRIM29 蛋白具有很高的序列同源性。DuTRIM29 以剂量依赖的方式抑制 IFN-β 和 IRF7 启动子的激活,并下调由 duRIG-I 介导的 IFN-β、IRF7、Mx 和 IL-6 的 mRNA 表达。此外,duTRIM29 在细胞质中与 duMAVS 相互作用并共定位。DuTRIM29 与其 C 末端结构域相互作用。此外,duTRIM29 抑制 IFN-β 和 IRF7 启动子的激活,并显著下调由 duMAVS 在鸭中介导的 IFN-β 和免疫相关基因的表达。此外,duTRIM29 诱导 K29 连接的多泛素化和 duMAVS 的降解,以抑制 IFN-β 的表达。总的来说,我们的结果表明,duTRIM29 通过靶向鸭 MAVS 负调控 I 型 IFN 的产生。这项研究将有助于更好地理解 TRIM 蛋白在鸭中调节先天免疫反应的分子机制。