数字农科院2.0

Methionine enkephalin upregulates toll-like receptors in macrophages to suppress severe fever with thrombocytopenia syndrome virus infection

文献类型： 外文期刊

作者： Jing Tian;Zhuping Ma;Xiaomeng Wang;Yonggang Li;Yulian Mu;Xiaoli Tao

作者机构：

关键词： macrophages;methionine enkephalin;RNA sequencing;severe fever with thrombocytopenia syndrome virus;toll-like receptors

期刊名称： Frontiers in Immunology

ISSN：

年卷期： 2025 年 16 卷

页码：

收录情况： SCIE（2025版）

摘要： Background: Severe fever with thrombocytopenia syndrome virus (SFTSV) is a newly identified tick-borne virus with a high case fatality rate. Currently, no specific antiviral drugs are available for its treatment. Methionine enkephalin (MENK) has the ability to enhance immune cell function nonspecifically. This study investigated the mechanism by which MENK regulates macrophages to exert antiviral effects against SFTSV infection. Methods: An SFTSV-infected RAW264.7 macrophage model pretreated with MENK was developed. RNA sequencing was employed to analyze transcriptomic alterations and identify differentially expressed genes (DEGs). Subsequent experimental validation based on bioinformatics analysis was performed on key DEGs. Results: The DEGs between the MENK–SFTSV and SFTSV groups were mainly enriched in several signaling pathways, including the Toll-like receptor (TLR) signaling pathway (ko04620), IL-17 signaling pathway (ko04657), TNF signaling pathway (ko04668), and interaction between viral proteins and cytokines and their receptors (ko04061). Key genes included TLR7, TLR3, TLR8, TLR9, activator protein-1 (AP-1), IL-17RA, TNF-α, IL-1β, CCR5, and CXCL10, all of which successfully docked with the MENK molecule. Compared with the TLR7 agonist imiquimod (IMQ), MENK demonstrated a greater advantage in modulating macrophages to resist SFTSV infection. MENK and the TLR7 agonist imiquimod can upregulate the expressions of TLR7, TLR3, AP-1, and IL-17RA. In addition, MENK significantly upregulated the levels of TLR9, TLR8, IL-1β, TNF-α, CCR5, and CXCL10. Conclusion: MENK upregulated the expression levels of the pattern recognition receptors and cytokine receptors; promoted the nuclear transcription to modulate cellular immune responses; and increased the levels of the cytokines to induce inflammatory responses against SFTSV infection. Notably, MENK possessed unique advantages and exhibited efficacy comparable to IMQ in restoring antiviral immunity, suggested that MENK emerged as a promising host-directed therapeutic candidate or vaccine prototype against SFTSV infection, warranting further preclinical and clinical investigation.

分类号：

  • 相关文献

[1]ModulationofmousemacrophageproteomeinducedbyToxoplasmagondiitachyzoitesinvivo. ZhouDonghui,YuanZiguo,ZhaoFurong,LiHailong,ZhouYang,LinRuiqing,ZouFengcai,SongHuiqun,XuMinjun,andZhuXingquan. 2011

[2]Transcript Profiling of Toll-Like Receptor mRNAs in Selected Tissues of Mink (Neovison vison). Tong, Mingwei,Yi, Li,Cheng, Yuening,Zhang, Miao,Cao, Zhigang,Wang, Jianke,Zhao, Hang,Lin, Peng,Cheng, Shipeng,Yang, Yong.

[3]Glycyrrhetinic acid extracted from Glycyrrhiza uralensis Fisch induces the expression of Toll-like receptor 4 in Ana-1 murine macrophages. Li, Li,Miao, Jian-Hua,Xu, Yong-Li,Peng, Li-Na,Qiu, Ya-Feng,Gao, Xiao-Qi,Shi, Zi-Xue,Shao, Dong-Hua,Wei, Jian-Chao,Ma, Zhi-Yong,Zhou, Ying. 2011

[4]Eimeria tenella: Expression profiling of toll-like receptors and associated cytokines in the cecum of infected day-old and three-week old SPF chickens. Cai, Jianping,Zhang, Lei,Liu, Renqiang,Ma, Liping,Wang, Yingwei,Pan, Baoliang,Wang, Ming. 2012

[5]Differential modulation of avian beta-defensin and Toll-like receptor expression in chickens infected with infectious bronchitis virus. Xu, Yang,Zhang, Tingting,Xu, Qianqian,Liang, Shuling,Ma, Deying,Han, Zongxi,Shao, Yuhao,Liu, Shengwang.

[6]Deletion of MyD88 adaptor in nociceptor alleviates low-dose formalin-induced acute pain and persistent pain in mice. Jiang, Zuo-Jie,Li, Qing-Yi,Zhang, Ying-Ying,Zeng, Mei-Xing,Hu, Han,Zhang, Feng-Ming,Bi, Ling-Bo,Gu, Jia-Hui,Liu, Xing-Jun. 2021

[7]The HPV viral regulatory mechanism of TLRs and the related treatments for HPV-associated cancers. Shi Yu Qi,Miao Miao Yang,Chong Yang Li,Kun Yu,Shou Long Deng. 2024

[8]Excretory/secretory proteome of 14-day schistosomula, Schistosoma japonicum. Cao, Xiaodan,Fu, Zhiqiang,Han, Qian,Lu, Ke,Li, Hao,Zhu, Chuangang,Hong, Yang,Lin, Jiaojiao,Lin, Jiaojiao,Zhang, Min,Han, Yanhui.

[9]Structural features and immunostimulating effects of three acidic polysaccharides isolated from Panax quinquefolius. Wang, Lijun,Yao, Yang,Sang, Wei,Yang, Xiushi,Ren, Guixing,Wang, Lijun.

[10]Proteomic alteration of equine monocyte-derived macrophages infected with equine infectious anemia virus. Du, Cheng,Liu, Hai-Fang,Lin, Yue-Zhi,Wang, Xue-Feng,Ma, Jian,Wang, Xiaojun,Zhou, Jian-Hua,Du, Cheng,Li, Yi-Jing,Zhou, Jian-Hua.

[11]Infection with equine infectious anemia virus vaccine strain EIAV(DLV121) causes no visible histopathological lesions in target organs in association with restricted viral replication and unique cytokine response. Liu, Qiang,Ma, Jian,Wang, Xue-Feng,Xiao, Fei,Li, Li-Jia,Zhang, Jiao-Er,Lin, Yue-Zhi,Du, Cheng,He, Xi-Jun,Wang, Xiaojun,Zhou, Jian-Hua,Zhou, Jian-Hua.

[12]The therapeutic potential for targeting CSE/H2S signaling in macrophages against Escherichia coli infection. Shaodong Fu,Zhenglei Wang,Xiangan Han,Yuanyuan Xu,Jinfeng Miao. 2023

[13]Rna‐seq analysis of influenza a virus‐induced transcriptional changes in mice lung and its possible implications for the virus pathogenicity in mice. Tianxin Ma,Abdou Nagy,Guanlong Xu,Lingxiang Xin,Danqi Bao,Chenyang Lu,Shiqi Niu,Zihua Wu,Chaochao Ren,Ting Zhang,Jianmei Yang,Qiaoyang Teng,Xuesong Li,Zejun Li,Qinfang Liu. 2021

[14]Uterine macrophages as treatment targets for therapy of premature rupture of membranes by modified ADSC-EVs through a circRNA/miRNA/NF-κB pathway. Yuhua Gao,Ningning Mi,Ying Zhang,Xiangchen Li,Weijun Guan,Chunyu Bai. 2022

[15]Modulation of Macrophage Polarization by Viruses: Turning Off/On Host Antiviral Responses. Shaoxiong Yu,Hailiang Ge,Su Li,Hua Ji Qiu. 2022

[16]Brucella induces heme oxygenase-1 expression to promote its infection. Hu, Hai,Tian, Mingxing,Yin, Yi,Zuo, Dong,Guan, Xiang,Ding, Chan,Yu, Shengqing. 2021

[17]Brucella rough RB51 infection activates P53-Slc7a11-Gpx4/GSH pathway to induce ferroptosis to attenuate the intracellular survival on macrophages. Hai Hu,Guangdong Zhang,Mingxing Tian,Yi Yin,Yanqing Bao,Xiang Guan,Chan Ding,Shengqing Yu. 2024

[18]Emerging insights into macrophage extracellular traps in bacterial infections. Ahmed Adel Baz,Huafang Hao,Shimei Lan,Zhangcheng Li,Shuang Liu,Xiangrui Jin,Shengli Chen,Yuefeng Chu. 2024

[19]CCL3 Promotes Cutaneous Wound Healing Through Recruiting Macrophages in Mice. Wanwan Shi,Xunsheng Li,Zhen Wang,Chenguang Li,Datao Wang,Chunyi Li. 2024

[20]Lactobacillus acidophilus protects against Corynebacterium pseudotuberculosis infection by regulating the autophagy of macrophages and maintaining gut microbiota homeostasis in C57BL/6 mice. Li, Dengliang,Jiang, Yuecai,Cui, Zhanding,Ma, Mengzhen,Zhu, Fang,Li, Guanhua,Yang, Haoyue,Li, Shaofei,Zhang, Tianliang,Chen, Dekun,Ma, Wentao. 2024

作者其他论文 更多>>