DC-SIGN在慢性乙型肝炎病毒感染时树突状细胞成熟活化中的作用

邹小静; 姜雪强; 田德英

DC-SIGN在慢性乙型肝炎病毒感染时树突状细胞成熟活化中的作用

华中科技大学同济医学院附属同济医院感染科

基金项目:

湖北省自然科学基金项目(2008CDA049)；

详细信息

中图分类号: R512.62
计量
- 文章访问数: 2705
- HTML全文浏览量: 14
- PDF下载量: 889
- 被引次数: 0
出版历程
- 出版日期: 2011-02-20

Role of DC-SIGN on the maturation and activation of dendritic cells in chronic hepatitis B virus infection

Research funding:

摘要

摘要: 目的研究慢性HBV感染时,DC-SIGN在树突状细胞（DC）成熟和活化中介导的作用。方法将α-甘露糖苷酶抑制剂-基夫碱作用于HepG2.2.15细胞,收获上清中的高甘露糖型HBV颗粒,并于第5 d加入到外周血单核细胞衍生的DC培养基中,培养至第7 d,采用流式细胞仪检测DC表面CDla、CD83、CD80、CD86、HLA-DR分子的表达,MTT法检测DC刺激淋巴细胞增殖的能力,ELISA法检测DC分泌IL-12的水平。结果高甘露糖型HBV组,与天然的HBV组相比,DC表面CDla、CD83、CD80、CD86、HLA-DR分子的表达增加,分泌IL-12的水平升高,刺激同种异体淋巴细胞增殖的能力亦明显增强,且上述效应均可被DC-SIGN特异性抗体所阻断。结论 DC-SIGN识别高甘露糖型HBV后可以促进DC的成熟和活化,天然的HBV可能利用α-甘露糖苷酶参与的去甘露聚糖修饰来逃避DC-SIGN的识别,从而诱导DC功能的缺陷。
- 肝炎,乙型,慢性 /
- 肝炎病毒,乙型 /
- 树突细胞
Abstract: Objective To investigate the role of DC-SIGN on the maturation and activation of dendritic cells (DC) in chronic HBV infection.Methods Highly mannosylated HBV obtained by treating HepG2.2.15 cells with the a-mannosidase I inhibitor kifunensine were added to the medium of DC derived from peripheral blood mononuclear cells on day 5 after culture.The expression rates of CDla, CD83, CD80, CD86 and HLA-DR of DCs were assayed by flow cytometry analysis, the stimulating capacity of DC was detected by MTT assay and the levels of IL-12 released by DCs were measured by ELISA on day 7.Results Compared with native HBV group, the expression of CDla, CD83, CD80, CD86 and HLA-DR of DC were significantly improved, levels of IL-12 were increased, and capacity of stimulating lymphocyte proliferation was enhanced in highly mannosylated HBV group.Furthermore these effects could be all blocked by DC-SIGN specific antibody.Conclusion DC-SIGN can promote the maturation and activation of DC after recognizing highly mannosylated HBV, native HBV may exploit demannosylation as a way to escape recognition by DC-SIGN and thereby induce DC dysfunction.
- hepatitis B /
- chronic /
- hepatitis B virus

HTML全文

参考文献(12)

[1]Wang FS, Xing LH, Liu MX, et al.Dysfunction of peripheral blood dendritic cells from patients with chronic hepatitis B virus infection[J].World J Gastroenterol, 2001, 7 (4) :537-541.

[2]Koppel EA, van Gisbergen KP, Geijtenbeek TB, et al.Distinct functions of DC-SIGN and its homologues L-SIGN (DC-SIGNR) and mSIGNR1 in pathogen recognition and immune regulation[J].Cell Microbiol, 2005, 7 (2) :157-165.

[3]Op den Brouw ML, de Jong MA, Ludwig IS, et al.Branched oligosaccharide structures on HBV prevent interaction with both DC-SIGN and L-SIGN[J].J Viral Hepat, 2008, 15 (9) :675-683.

[4]Treuheit MJ, Kosky AA, Brems DN.Inverse relationship of protein concentration and aggregation[J].Pharm Res, 2002, 19 (4) :511-516.

[5]Duperrier K, Eljaafari A, Dezutter-Dambuyant C, et al.Distinct subsets of dendritic cells resembling dermal DCs can be generated in vitro from monocytes, in the presence of different serum supplements[J].J Immunol Methods, 2000, 238 (1-2) :119-131.

[6]Van Montfort T, Nabatov AA, Geijtenbeek TB, et al.Efficient capture of antibody neutralized HIV-1 by cells expressing DC-SIGN and transfer to CD4+T lymphocytes[J].J Immunol, 2007, 178 (5) :3177-3185.

[7]Geijtenbeek TB, Van Vliet SJ, Koppel EA, et al.Mycobacteria target DC-SIGN to suppress dendritic cell function[J].J Exp Med, 2003, 197 (1) :7-17.

[8]Wei X, Decker JM, Wang S, et al.Antibody neutralization and escape by HIV-1[J].Nature, 2003, 422 (6929) :307-312.

[9]Lee J, Park JS, Moon JY, et al.The influence of gly-cosylation on secretion, stability, and immunogenicity of recombinant HBV pre-S antigen synthesized in Saccharomyces cerevisiae[J].Biochem Biophys Res Commun, 2003, 303 (2) :427-432.

[10]Liu M, Chen H, Luo F, et al.Deletion of N-glycosylation sites of hepatitis C virus envelope protein E1 enhances specific cellular and humoral immune responses[J].Vaccine, 2007, 25 (36) :6572-6580.

[11]Brown KS, Ryder SD, Irving WL, et al.Mannan binding lectin and viral hepatitis[J].Immunol Lett, 2007, 108 (1) :34-44.

[12]Hering KW, Karaveg K, Moremen KW, et al.A practical synthesis of kifunensine analogues as inhibitors of endoplasmic reticulum alpha-mannosidase I[J].J Org Chem, 2005, 70 (24) :9892-9904.

施引文献

资源附件(0)

访问统计