CLEC4M介导HCV负载后树突状细胞的功能变化

朱婷; 赵西太; 聂青和; 龙振昼; 高禄化; 王媛媛

doi:10.3969/j.issn.1001-5256.2017.06.017

CLEC4M介导HCV负载后树突状细胞的功能变化

DOI: 10.3969/j.issn.1001-5256.2017.06.017

1. 第四军医大学唐都医院传染病科全军感染病诊疗中心
2. 西安市第八医院

基金项目:

国家自然科学基金(81170390)；

详细信息

中图分类号: R512.63
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出版历程
- 出版日期: 2017-06-20

Changes in the function of dendritic cells after HCV loading mediated by CLEC4M

Research funding:

摘要

摘要: 目的通过检测树突状细胞（DC）黏附HCV后的功能变化,探索CLEC4M介导HCV黏附DC的可能机制,初步揭示CLEC4M对DC介导的固有免疫应答的影响。方法提取正常人外周血单个核细胞,并诱导分化为成熟DC,流式细胞术检测DC表面CLEC4M的表达情况。利用制备好的HCVcc病毒液感染成熟DC,并设置阳性对照组、甘露聚糖干扰组、CLEC4M单抗干扰组和空白对照组,分别收集感染各组的细胞上清液,采用ELISA法检测各组细胞上清液中IL-10与IL-12p70的水平变化。计量资料多组间比较采用单因素方差分析,进一步两组间比较采用LSD-t检验。结果 DC表面CLEC4M的表达阳性率高达82.6%。ELISA法检测各组细胞上清IL-10、IL-12p70的水平,4组间比较差异有统计学意义（F值分别为54.46、77.72,P值均<0.001）,其中阳性对照组中IL-10、IL-12p70的表达水平明显高于两干扰组（P值均<0.001）,阳性对照组、两干扰组IL-10、IL-12p70的水平均高于空白对照组（P值均<0.001）。结论 CLEC4M介导了HCV黏附DC,参与机体...
- 肝炎病毒属 /
- 树突细胞 /
- 外源凝集素类,C型
Abstract: Objective To investigate the changes in the function of dendritic cells (DCs) after HCV adherence, possible mechanisms of HCV adherence of DCs mediated by CLEC4 M, and the impact of CLEC4 M on innate immune response mediated by DCs. Methods Peripheral blood mononuclear cells (PBMCs) were isolated from healthy people and induced to differentiate into mature DCs. Flow cytometry was used to measure the expression of CLEC4 M on the surface of DCs. Mature DCs were infected by HCVcc and positive control group, mannan interference group, CLEC4 M monoclonal antibody interference group, and blank control group were established. The supernatant was collected from each infected group, and ELISA was used to measure the changes in the levels of interleukin-10 (IL-10) and interleukin-12p70 (IL-12p70) in supernatant. A one-way analysis of variance was used for comparison of continuous data between multiple groups, and the least significant difference t-test was used for further comparison between any two groups. Results The positive rate of CLEC4 M in the surface of DCs reached 82. 6%. There were significant differences in the levels of IL-10 and IL-12p70 between the groups (F =54. 46 and 77. 72, both P < 0. 001) . The positive control group had significantly higher levels of IL-10 and IL-12p70 than the two interference groups (all P < 0. 001) , and compared with the blank control group, the positive control group, CLEC4 M monoclonal antibody interference group, and mannan interference group had significantly higher levels of IL-10 and IL-12p70 (all P < 0. 001) . Conclusion CLEC4 M mediates HCV adherence of DCs, participates in the body's immune response, and regulate the expression of DC immune molecules.
- hepacivirus /
- dendritic cells /
- lectins, C-Type

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参考文献(21)

[1]DAW MA, El-BOUZEDI AA, AHMEDMO, et al.Geographic integration of hepatitis C virus:a global threat[J].World J Virol, 2016, 5 (4) :170-182.

[2]ALBECKA A, BELOUZARD S, OP DE BEECK A, et al.Role of low-density lipoprotein receptor in the hepatitis C virus life cycle[J].Hepatology, 2012, 55 (4) :998-1007.

[3]WANG YY, NIE QH, GAO LH.The in vitro study of HCV infected of human dendritic cells interfered by CLEC4M[J].Chin Hepatol, 2013, 18 (4) :231-234. (in Chinese) 王媛媛, 聂青和, 高禄化.CLEC4M介导HCV感染人PBDC实验研究[J].肝脏, 2013, 18 (4) :231-234.

[4]LAI WK, SUN PJ, ZHANG J, et al.Expression of DC-SIGN and DC-SIGNR on human sinusoidal endothelium:a role for capturing hepatitis C virus particles[J].Am J Pathol, 2006, 169 (1) :200-208.

[5]CROSIGNANI A, RIVA A, DELLA BELLA S.Analysis of peripheral blood dendritic cells as a non-invasive tool in the follow-up of patients with chronic hepatitis C[J].World J Gastroenterol, 2016, 22 (4) :1393-1404.

[6]CORMIER EG, DURSO RJ, TSAMIS F, et al.L-SIGN (CD209L) and DC-SIGN (CD209) mediate transinfection of liver cells by hepatitis C virus[J].Proc Natl Acad Sci U S A, 2004, 101 (39) :14067-14072.

[7]LINDENBACH BD, EVANS MJ, SYDER AJ, et al.Complete replication of hepatitis C virus in cell culture[J].Science, 2005, 309 (5734) :623-626.

[8]ZHU T, NIE QH, WANG YY, et al.Influence of C-type lectin domain family 4, member M (CLEC4M) on the susceptibility of Huh7.5 cells to HCVcc[J].Chin Hepatol, 2015, 20 (3) :205-209. (in Chinese) 朱婷, 聂青和, 王媛媛, 等.C型凝集素CLEC4M对HCVcc易感性的影响[J].肝脏, 2015, 20 (3) :205-209.'

[9]VAN DER AA E, van de LAAR L, JANSSEN HL, et al.BDCA3expression is associated with high IFN-λproduction by CD34+-derived dendritic cells generated in the presence of GM-CSF, IL-4, and/or TGF-β[J].Eur J Immunol, 2015, 45 (5) :1471-1481.

[10]SCHRAML BU, REIS E SOUSA C.Defining dendritic cells[J].Curr Opin Immunol, 2015, 32 (1) :13-20.

[11]CHEN PC, CHUANG PK, CHEN CH, et al.Role of N-linked glycans in the interactions of recombinant HCV envelope glycoproteins with cellular receptors[J].ACS Chem Biol, 2014, 9 (7) :1437-1443.

[12]LOZACH PY, LORTAT-JACOB H, de LACROIX DE LAVALETTE A, et al.DC-SIGN and L-SIGN are high affinity binding receptors for hepatitis C virus glycoprotein E2[J].J Biol Chem, 2003, 278 (22) :20358-20366.

[13]SACHDEVA M, CHAWLA YK, ARORA SK.Dendritic cells:The warriors upfront-turned defunct in chronic hepatitis C infection[J].World J Hepatol, 2015, 7 (19) :2202-2208.

[14]MASON CP, TARR AW.Human lectins and their roles in viral infections[J].Molecules, 2015, 20 (2) :2229-2271.

[15]BANG BR, ELMASRY S, SAITO T.Organ system view of the hepatic innate immunity in HCV infection[J].J Med Virol, 2016, 88 (12) :2025-2037.

[16]MA X, YAN W, ZHENG H, et al.Regulation of IL-10 and IL-12 production and function in macrophages and dendritic cells[J].F1000Res, 2015.

[17]MAYNARD CL, WEAVER CT.Diversity in the contribution of interleukin-10 to T-cell-mediated immune regulation[J].Immunol Rev, 2008, 226 (1) :219-233.

[18]GEGIANAT J, NIZZOLI G, PARONI M, et al.Immunity to pathogens taught by specialized human dendritic cell Subsets[J].Front Immunol, 2015, 6 (527) :1-13.

[19]MCGOVERN N, SCHLIZER A, GUNAWAN M, et al.Human dermal CD14+cells are a transient population of monocyte-derived macrophages[J].Immunity, 2014, 41 (3) :465-477.

[20]NIE QH, GAO LH, CENG YQ, et al.Hepatitis C virus infection of human cytotrophoblasts cultured in vitro[J].J Med Virol, 2012, 84 (10) :1586-1592.

[21]BOSE M, MULLICK R, DAS S, et al.Combination of neutralizing monoclonal antibodies against Hepatitis C virus E2 protein effectively blocks virus infection[J].Virus Res, 2016, 224 (1) :46-57.

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