Hepatitis C virus E2 and CD81 interaction may be associated with altered trafficking of dendritic cells in chronic hepatitis C
Hepatitis C virus E2 and CD81 interaction may be associated with altered trafficking of dendritic cells in chronic hepatitis C
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DOI：
10.1002/hep.21350
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发表时间：
2006-10-01
期刊：
影响因子：
13.5
通讯作者：
Spengler, Ulrich
中科院分区：
文献类型：
--
作者：
Nattermann, Jacob;Zimmermann, Henning;Spengler, Ulrich
树突状细胞(DC)在诱导免疫反应中起着至关重要的作用；然而，关于DC在慢性丙型肝炎中的作用的报道仍存在争议。DC的功能包括在感染部位和淋巴细胞室之间进行适当的细胞运输。因此，我们分析了丙型肝炎病毒感染患者的DC区划和DC迁移的变化。我们发现丙型肝炎病毒(+)患者(n=20)外周血中BDCA1+和BDCA2+DC数量显著低于健康对照组(n=12)(P<；0.05)。分析15例丙型肝炎病毒(+)患者、15例丙型肝炎病毒(-)对照组和10例疾病对照组的肝脏样本，我们发现慢性丙型肝炎与肝内树突状细胞的浓缩有关(P<；0.05)。体外研究表明，丙型肝炎病毒E2诱导的RANTES的分泌能有效地吸引CCR5(+)的未成熟DC。DC与来自丙型肝炎病毒(+)患者的血清孵育，使DC对CCL21无反应，CCL21是一种趋化因子，将DC募集到淋巴组织中进行T细胞免疫。与通过RANTES吸引CCR5+DC不同，CCL21对DC迁移的直接抑制是慢性丙型肝炎患者所特有的，这可能归因于HCVE2与DC上CD81的相互作用。总之，CD81与丙型肝炎病毒E2的相互作用显著影响DC的迁移。DC不能再循环到淋巴组织可能是丙型肝炎病毒感染过程中T细胞启动受损的重要原因。
Dendritic cells (DC) are crucially involved in the induction of immune responses; however, reports on DC functions in chronic hepatitis C are controversial. Function of DC includes proper cell trafficking between sites of infection and lympho-cellular compartments. Thus, we analyzed DC compartmentalization and changes in DC migration in hepatitis C virus (HCV)-infected patients. We found significantly lower numbers of circulating BDCA1+ and BDCA2+ DC in HCV(+) patients (n = 20) than in healthy controls (n = 12) (P < .05). Analyzing liver samples from HCV(+) patients (n = 15), HCV(-) controls (n = 15), and disease controls (n = 10), we demonstrated chronic hepatitis C to be associated with intrahepatic DC enrichment (P < .05). In vitro studies indicated that HCV E2-induced secretion of RANTES efficiently attracts CCR5(+) immature DC. Incubation of DC with sera derived from HCV(+) patients made DC unresponsive to CCL21, the chemokine recruiting DC to lymphoid tissues for T cell priming. Unlike attraction of CCR5 + DCs via RANTES, direct inhibition of DC migration in response to CCL21 was specific for patients with chronic hepatitis C and could be attributed to interaction of HCV E2 with CD81 on DC. In conclusion, migration of DC is markedly affected by interaction of HCV E2 with CD81. Failure of DC to recirculate to lymphoid tissue may be critically involved in impaired T cell priming during HCV infection.