Choi Byungyoon, Park Woo-Ram, Kim Yu-Ji, Mun Seulgi, Park Su-Jin, Jeong Jae-Ho, Choi Hueng-Sik, Kim Don-Kyu
Department of Integrative Food, Bioscience and Biotechnology, Chonnam National University, Gwangju, 61186, Republic of Korea.
Department of Applied Biology, Chonnam National University, Gwangju, 61186, Republic of Korea.
Insect Biochem Mol Biol. 2022 Sep;148:103816. doi: 10.1016/j.ibmb.2022.103816. Epub 2022 Aug 1.
Antimicrobial peptides (AMPs) are core components of innate immunity to protect insects against microbial infections. Nuclear receptors (NRs) are ligand-dependent transcription factors that can regulate the expression of genes critical for insect development including molting and metamorphosis. However, the role of NRs in host innate immune response to microbial infection remains poorly understood in Tribolium castaneum (T. castaneum). Here, we show that estrogen-related receptor (ERR), an insect ortholog of the mammalian ERR family of NRs, is a novel transcriptional regulator of AMP genes for innate immune response of T. castaneum. Tribolium ERR (TcERR) expression was induced by immune deficiency (IMD)-Relish signaling in response to infection by Escherichia coli (E. coli), a Gram-negative bacterium, as demonstrated in TcIMD-deficient beetles. Interestingly, genome-wide transcriptome analysis of TcERR-deficient old larvae using RNA-sequencing analysis showed that TcERR expression was positively correlated with gene transcription levels of AMPs including attacins, defensins, and coleoptericin. Moreover, chromatin immunoprecipitation analysis revealed that TcERR could directly bind to ERR-response elements on promoters of genes encoding defensin3 and coleoptericin, critical for innate immune response of T. castaneum. Finally, TcERR-deficient old larvae infected with E. coli displayed enhanced bacterial load and significantly less host survival. These findings suggest that TcERR can coordinate transcriptional regulation of AMPs and host innate immune response to bacterial infection.
抗菌肽（AMPs）是昆虫先天免疫的核心组成部分，可保护昆虫免受微生物感染。核受体（NRs）是依赖配体的转录因子，可调节对昆虫发育至关重要的基因的表达，包括蜕皮和变态。然而，在赤拟谷盗（Tribolium castaneum，T. castaneum）中，NRs在宿主对微生物感染的先天免疫反应中的作用仍知之甚少。在此，我们表明雌激素相关受体（ERR）是哺乳动物ERR家族NRs的昆虫直系同源物，是T. castaneum先天免疫反应中AMP基因的新型转录调节因子。如在TcIMD缺陷型甲虫中所证明的，免疫缺陷（IMD）-Relish信号通路在受到革兰氏阴性细菌大肠杆菌（E. coli）感染时可诱导赤拟谷盗ERR（TcERR）的表达。有趣的是，使用RNA测序分析对TcERR缺陷型老龄幼虫进行全基因组转录组分析表明，TcERR的表达与包括attacins、defensins和coleoptericin在内的AMPs的基因转录水平呈正相关。此外，染色质免疫沉淀分析表明，TcERR可直接结合到编码defensin3和coleoptericin的基因启动子上的ERR反应元件上，这对T. castaneum的先天免疫反应至关重要。最后，感染大肠杆菌的TcERR缺陷型老龄幼虫表现出细菌载量增加，宿主存活率显著降低。这些发现表明，TcERR可以协调AMPs的转录调控和宿主对细菌感染的先天免疫反应。
