Toll样受体7在抗感染免疫中的作用

doi:10.12140/j.issn.1000-7423.2022.01.015

摘要/Abstract

摘要：

Toll样受体7(Toll-like receptor 7,TLR7)是一种模式识别受体,细胞静息状态下主要定位于浆细胞样树突状细胞、巨噬细胞、T淋巴细胞、中性粒细胞等免疫细胞,以及上皮细胞、内皮细胞、角质形成细胞等非免疫细胞的内质网上。病原体感染时,TLR7从内质网转移到效应细胞的内体膜上。TLR7可直接识别单链RNA或核酸类似物等配体,与特异性招募蛋白结合并激活核因子-κB、丝裂原活化蛋白激酶和干扰素等调控因子,从而启动固有免疫应答和适应性免疫应答,参与抗感染免疫。本文就TLR7及其配体的结构与功能、TLR7在抗感染免疫中的作用及其相关信号通路等进行综述,以期为TLR7在抗感染免疫中的作用机制研究提供科学依据。

关键词: Toll样受体7, 抗感染, 免疫应答, 分子机制

Abstract:

Toll-like receptor 7 (TLR7) is a pattern recognition receptor mainly expressed in the endoplasmic reticulum of the resting immune cells including plasmacytoid dendritic cell, mononuclear macrophages, T lymphocytes, neutrophils and non-immune cells including epithelial cells, endothelial cells and keratinocytes. During an infection, TLR7 is translocated to the endosome membrane from endoplasmic reticulum of the host cells. TLR7 can directly recognize single-stranded RNA or nucleic acid analogs and bind to specific recruiting proteins to activate nuclear factor-κB, mitogen-activated protein kinase and interferon regulatory factors, which eventually triggers the innate or adaptive immune response against an infection. Here we have reviewed the structure and function of TLR7 and its ligand, the role of TLR7 against an infection and its signaling pathways to provide the scientific basis for further studies of TLR7 in infection and immunity.

Key words: Toll-like receptor 7, Anti-infection, Immune response, Molecular mechanism

中图分类号:

尹昌竹, 李迪, 蔡娟, 徐红玲, 王灵军, 郑明辉, 刘晖. Toll样受体7在抗感染免疫中的作用[J]. 中国寄生虫学与寄生虫病杂志, 2022, 40(1): 99-103.

YIN Chang-zhu, LI Di, CAI Juan, XU Hong-ling, WANG Ling-jun, ZHENG Ming-hui, LIU Hui. Role of Toll-like receptor 7 in anti-infective immunity[J]. Chinese Journal of Parasitology and Parasitic Diseases, 2022, 40(1): 99-103.

参考文献 49

[1]	Pachathundikandi SK, Lind J, Tegtmeyer N, et al. Interplay of the gastric pathogen Helicobacter pylori with toll-like receptors[J]. Biomed Res Int, 2015, 2015: 192420. doi: 10.1155/2015/192420 pmid: 25945326
[2]	Du X, Poltorak A, Wei Y, et al. Three novel mammalian toll-like receptors: gene structure, expression, and evolution[J]. Eur Cytokine Netw, 2000, 11(3): 362-371. pmid: 11022119
[3]	Petes C, Odoardi N, Gee K. The toll for trafficking: toll-like receptor 7 delivery to the endosome[J]. Front Immunol, 2017, 8: 1075. doi: 10.3389/fimmu.2017.01075
[4]	Yin T, He S, Wang Y. Toll-like receptor 7/8 agonist, R848, exhibits antitumoral effects in a breast cancer model[J]. Mol Med Rep, 2015, 12(3): 3515-3520. doi: 10.3892/mmr.2015.3885
[5]	Chen H, Cheng ZY, Pan Y, et al. RASAL1 influences the proliferation and invasion of gastric cancer cells by regulating the RAS/ERK signaling pathway[J]. Hum Cell, 2014, 27(3): 103-110. doi: 10.1007/s13577-014-0090-2
[6]	Dong GJ, Si CP. The role of IFN-α in the initiation and development of SLE[J]. J Jining Med Univ, 2016, 39(1): 6-11. (in Chinese)
	(董冠军, 司传平. IFN-α在SLE发生发展中的作用[J]. 济宁医学院学报, 2016, 39(1), 39: 6-11.)
[7]	Chuang TH, Ulevitch RJ. Cloning and characterization of a sub-family of human toll-like receptors: hTLR7, hTLR8 and hTLR9[J]. Eur Cytokine Netw, 2000, 11(3): 372-378. pmid: 11022120
[8]	Celhar T, Pereira-Lopes S, Thornhill SI, et al. TLR7 and TLR9 ligands regulate antigen presentation by macrophages[J]. Int Immunol, 2016, 28(5): 223-232. doi: 10.1093/intimm/dxv066 pmid: 26567289
[9]	Takeuchi O, Akira S. Pattern recognition receptors and inflammation[J]. Cell, 2010, 140(6): 805-820. doi: 10.1016/j.cell.2010.01.022 pmid: 20303872
[10]	Wu H, Wu XM. Anti-HBV activity of TLR7 ligand Loxoribine in vitro[J]. Guangdong Med J, 2010, 31(3): 287-289. (in Chinese)
	(吴红, 吴晓蔓. TLR7配体Loxoribine抗乙型肝炎病毒的体外实验研究[J]. 广东医学, 2010, 31(3): 287-289.)
[11]	Goff PH, Hayashi T, He WQ, et al. Syntheti toll-like receptor 4 (TLR4) and TLR7 ligands work additively via MyD88 to induce protective antiviral immunity in mice[J]. J Virol, 2017, 91(19): e01050-17.
[12]	Kim SJ, Chen Z, Essani AB, et al. Identification of a novel toll-like receptor 7 endogenous ligand in rheumatoid arthritis synovial fluid that can provoke arthritic joint inflammation[J]. Arthritis Rheumatol, 2016, 68(5): 1099-1110.
[13]	Mukherjee S, Huda S, Sinha Babu SP. Toll-like receptor polymorphism in host immune response to infectious diseases: a review[J]. Scand J Immunol, 2019, 90(1): e12771.
[14]	Wei W. Research of immune activation by HCV via TLR7 and function analyse for TLR7 cytoplasmic domain[D]. Shanghai: Second Military Medical University, 2011: 1. (in Chinese)
	(魏伟. TLR7在HCV感染过程中的免疫激活及胞内区功能研究[D]. 上海: 第二军医大学, 2011: 1.)
[15]	Hofmann H, Vanwalscappel B, Bloch N, et al. TLR7/8 agonist induces a post-entry SAMHD1-independent block to HIV-1 infection of monocytes[J]. Retrovirology, 2016, 13(1): 83. doi: 10.1186/s12977-016-0316-3
[16]	Pavlovic M, Gross C, Chili C, et al. MAIT cells display a specific response to type 1 IFN underlying the adjuvant effect of TLR7/8 ligands[J]. Front Immunol, 2020, 11: 2097. doi: 10.3389/fimmu.2020.02097 pmid: 33013883
[17]	Caetano BC, Carmo BB, Melo MB, et al. Requirement of UNC93B1 reveals a critical role for TLR7 in host resistance to primary infection with Trypanosoma cruzi[J]. J Immunol, 2011, 187(4): 1903-1911. doi: 10.4049/jimmunol.1003911
[18]	Jiang YY, Xu YX, Yuan ZY, et al. Effect of toll-like receptor(TLR) 7 deficiencies on the in vivo immune response against Schistosoma japonicum[J]. Chin J Parasitol Parasit Dis, 2014, 32(3): 172-175. (in Chinese)
	(姜岩岩, 徐馀信, 袁忠英, 等. Toll样受体7敲除对日本血吸虫感染早期免疫应答的影响[J]. 中国寄生虫学与寄生虫病杂志, 2014, 32(3): 172-175.)
[19]	Ordeix L, Montserrat-Sangrà S, Martínez-Orellana P, et al. Toll-like receptors 2, 4 and 7, interferon-gamma and interleukin 10, and programmed death ligand 1 transcripts in skin from dogs of different clinical stages of leishmaniosis[J]. Parasit Vectors, 2019, 12(1): 575. doi: 10.1186/s13071-019-3827-7 pmid: 31806038
[20]	Regli IB, Passelli K, Martínez-Salazar B, et al. TLR7 sensing by neutrophils is critical for the control of cutaneous leishmaniasis[J]. Cell Rep, 2020, 31(10): 107746. doi: S2211-1247(20)30726-9 pmid: 32521271
[21]	Gao W, Sun X, Li D, et al. Toll-like receptor 4, Toll-like receptor 7 and toll-like receptor 9 agonists enhance immune responses against blood-stage Plasmodium chabaudi infection in BALB/c mice[J]. Int Immunopharmacol, 2020, 89(pt b): 107096. doi: 10.1016/j.intimp.2020.107096
[22]	Luo Q. Research on the effects and mechanism of TLR7 in invasive pulmonary aspergillosis[D]. Chongqing: Chongqing Medical University, 2020: 5-10. (in Chinese)
	(罗琴. Toll样受体7 (TLR7) 在侵袭性肺曲霉病中的作用及机制研究[D]. 重庆: 重庆医科大学, 2020: 5-10.)
[23]	Szabo A, Magyarics Z, Pazmandi K, et al. TLR ligands upregulate RIG-Ⅰ expression in human plasmacytoid dendritic cells in a typeⅠ IFN-independent manner[J]. Immunol Cell Biol, 2014, 92(8): 671-678. doi: 10.1038/icb.2014.38
[24]	de Marcken M, Dhaliwal K, Danielsen AC, et al. TLR7 and TLR8 activate distinct pathways in monocytes during RNA virus infection[J]. Sci Signal, 2019, 12(605): eaaw1347.
[25]	Thompson MR, Kaminski JJ, Kurt-Jones EA, et al. Pattern recognition receptors and the innate immune response to viral infection[J]. Viruses, 2011, 3(6): 920-940. doi: 10.3390/v3060920 pmid: 21994762
[26]	Hao WZ, Wang LY, Li ST. FKBP5 regulates RIG-I-mediated NF-κB activation and influenza a virus infection[J]. Viruses, 2020, 12(6): 672. doi: 10.3390/v12060672
[27]	Long SQ, Shang ZL, Zuo L. The research of the polarization and the expression of TLR7 by Ana-1 cell infected with DEN2[J]. Chin J Immunol, 2013, 29(7): 675-680. (in Chinese)
	(龙世棋, 商正玲, 左丽. 登革2型病毒体外诱导Ana-1巨噬细胞极化及其TLR7表达的研究[J]. 中国免疫学杂志, 2013, 29(7): 675-680.)
[28]	Posadas-Mondragón A, Aguilar-Faisal JL, Zuñiga G, et al. Association of genetic polymorphisms in TLR3, TLR4, TLR7, and TLR8 with the clinical forms of dengue in patients from Veracruz, Mexico[J]. Viruses, 2020, 12(11): 1230. doi: 10.3390/v12111230
[29]	Saha B, Kodys K, Adejumo A, et al. Circulating and exosome-packaged hepatitis C single-stranded RNA induce monocyte differentiation via TLR7/8 to polarized macrophages and fibrocytes[J]. J Immunol, 2017, 198(5): 1974-1984. doi: 10.4049/jimmunol.1600797
[30]	Zhang Y, El-Far M, Dupuy FP, et al. HCV RNA activates APCs via TLR7/TLR8 while virus selectively stimulates macrophages without inducing antiviral responses[J]. Sci Rep, 2016, 6: 29447. doi: 10.1038/srep29447
[31]	Sanjuan MA, Dillon CP, Tait SW, et al. Toll-like receptor signalling in macrophages links the autophagy pathway to phagocytosis[J]. Nature, 2007, 450(7173): 1253-1257. doi: 10.1038/nature06421
[32]	Sil P, Muse G, Martinez J. A ravenous defense: canonical and non-canonical autophagy in immunity[J]. Curr Opin Immunol, 2018, 50: 21-31. doi: 10.1016/j.coi.2017.10.004
[33]	Delgado MA, Deretic V. Toll-like receptors in control of immunological autophagy[J]. Cell Death Differ, 2009, 16(7): 976-983. doi: 10.1038/cdd.2009.40 pmid: 19444282
[34]	Ma QM, Han L, Deng GC, et al. The research progress of autophagy in Mycobacterium tuberculosis infection[J]. Chin J Cell Biol, 2019, 41(9): 1797-1804. (in Chinese)
	(马沁梅, 韩璐, 邓光存, 等. 自噬在结核分枝杆菌感染中作用的研究进展[J]. 中国细胞生物学学报, 2019, 41(9): 1797-1804.)
[35]	Franco LH, Fleuri AKA, Pellison NC, et al. Autophagy downstream of endosomal Toll-like receptor signaling in macrophages is a key mechanism for resistance to Leishmania major infection[J]. J Biol Chem, 2017, 292(32): 13087-13096. doi: 10.1074/jbc.M117.780981 pmid: 28607148
[36]	Zhou DJ, Kang KH, Spector SA. Production of interferon α by human immunodeficiency virus type 1 in human plasmacytoid dendritic cells is dependent on induction of autophagy[J]. J Infect Dis, 2012, 205(8): 1258-1267. doi: 10.1093/infdis/jis187
[37]	Herath K, Kim HJ, Lee JH, et al. Sargassum horneri (Turner) C. Agardh containing polyphenols attenuates particulate matter-induced inflammatory response by blocking TLR-mediated MYD88-dependent MAPK signaling pathway in MLE-12 cells[J]. J Ethnopharmacol, 2021, 265: 113340. doi: 10.1016/j.jep.2020.113340
[38]	Swiecki M, Colonna M. The multifaceted biology of plasmacytoid dendritic cells[J]. Nat Rev Immunol, 2015, 15(8): 471-485. doi: 10.1038/nri3865
[39]	Wang Y, Li J, Yan W, et al. An active component containing pterodontic acid and pterodondiol isolated from Laggera pterodonta inhibits influenza a virus infection through the TLR7/MyD88/TRAF6/NF-κB signaling pathway[J]. Mol Med Rep, 2018, 18(1): 523-531.
[40]	Yang BY, Cheng YG, Liu Y, et al. Datura metel L. ameliorates imiquimod-induced psoriasis-like dermatitis and inhibits inflammatory cytokines production through TLR7/8-MyD88-NF-κB-NLRP3 inflammasome pathway[J]. Molecules, 2019, 24(11): 2157. doi: 10.3390/molecules24112157
[41]	Auderset F, Belnoue E, Mastelic-Gavillet B, et al. A TLR7/8 agonist-including DOEPC-based cationic liposome formulation mediates its adjuvanticity through the sustained recruitment of highly activated monocytes in a type I IFN-independent but NF-κB-dependent manner[J]. Front Immunol, 2020, 11: 580974. doi: 10.3389/fimmu.2020.580974
[42]	Yap XZ, Lundie RJ, Beeson JG, et al. Dendritic cell responses and function in malaria[J]. Front Immunol, 2019, 10: 357. doi: 10.3389/fimmu.2019.00357
[43]	Cao W, Manicassamy S, Tang H, et al. Toll-like receptor-mediated induction of type I interferon in plasmacytoid dendritic cells requires the rapamycin-sensitive PI(3)K-mTOR-p70S6K pathway[J]. Nat Immunol, 2008, 9(10): 1157-1164. doi: 10.1038/ni.1645
[44]	Mahmoud HA, Mahmoud HH, Solahaye KS, et al. Activation toll-like receptor7 (TLR7) responsiveness associated with mitogen-activated protein kinase (MAPK) activation in HIOEC cell line of oral squamous cell carcinoma[J]. J Dent (Shiraz), 2018, 19(3): 217-224.
[45]	Funk E, Kottilil S, Gilliam B, et al. Tickling the TLR7 to cure viral hepatitis[J]. J Transl Med, 2014, 12: 129. doi: 10.1186/1479-5876-12-129
[46]	Kawai T, Akira S. Innate immune recognition of viral infection[J]. Nat Immunol, 2006, 7(2): 131-137. doi: 10.1038/ni1303 pmid: 16424890
[47]	Zhu Y, Shao Y, Qu X, et al. Sodium ferulate protects against influenza virus infection by activation of the TLR7/9-MyD88-IRF7 signaling pathway and inhibition of the NF-κB signaling pathway[J]. Biochem Biophys Res Commun, 2019, 512(4): 793-798. doi: 10.1016/j.bbrc.2019.03.113
[48]	Mancuso G, Gambuzza M, Midiri A, et al. Bacterial recognition by TLR7 in the lysosomes of conventional dendritic cells[J]. Nat Immunol, 2009, 10(6): 587-594. doi: 10.1038/ni.1733
[49]	Xie CL, Liu CY, Lin Y, et al. Effects of IRF1 on polarization and antitumor function of M1 microphage[J]. Basic Clin Med, 2017, 37(2): 189-196. (in Chinese)
	(谢昌利, 刘翠颖, 林艳, 等. IRF1对M1巨噬细胞极化及其抗肿瘤效应的影响[J]. 基础医学与临床, 2017, 37(2): 189-196.)