Inhibition of antigen-presenting cell functions by alcohol: implications for hepatitis C virus infection.
Inhibition of antigen-presenting cell functions by alcohol: implications for hepatitis C virus infection.
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酒精抑制抗原呈递细胞功能：对丙型肝炎病毒感染的影响。
DOI：
10.1016/j.alcohol.2004.07.003
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发表时间：
2004
期刊：
影响因子：
--
通讯作者：
White,Bernadette
中科院分区：
文献类型：
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作者：
Szabo,Gyongyi;Dolganiuc,Angela;Mandrekar,Pranoti;White,Bernadette
酒精诱导的免疫抑制机制包括先天和适应性免疫反应的缺陷。单核细胞和树突状细胞（dc）通过识别病毒抗原和诱导抗原特异性t细胞活化来连接先天和适应性免疫反应。我们研究了酒精对抗原提呈细胞功能的影响。健康志愿者急性饮酒（伏特加，2 ml/kg）导致单核细胞来源的dc抗原呈递细胞功能显著降低。在混合淋巴细胞培养中，酒精处理的DCs体外异源刺激能力降低与共刺激分子（B7.1和B7.2）表达降低以及白细胞介素(IL)-12降低和IL-10浓度升高相关。树突状细胞识别丙型肝炎病毒（HCV）感染中的病毒抗原，并且HCV疾病在酒精依赖个体中加速。对于慢性HCV感染患者，我们发现髓系dc的同种刺激能力降低。此外，对hcv感染患者获得的DC进行体外酒精处理后，DC功能降低，支持病毒因子和酒精可能相互作用双重抑制DC功能的建议。我们发现，用脂多糖诱导成熟并不能完全改善由酒精治疗、HCV感染或两者联合引起的DC异源刺激能力降低。此外，含有酒精处理的树突状细胞或hcv感染患者的树突状细胞的混合淋巴细胞培养物的上清液中的可溶性因子可以转移对健康志愿者的树突状细胞培养物中t细胞增殖的抑制作用。抗il -10中和抗体改善了hcv感染患者dc混合淋巴细胞反应的减少，而外源性IL-12治疗，而非抗il -10治疗，改善了健康志愿者dc酒精治疗诱导的t细胞增殖减少。我们的研究结果支持急性酒精摄入和体外酒精治疗均抑制DC抗原呈递细胞功能的建议，并支持病毒因子与酒精相互作用以降低HCV感染中DC功能的假设。
The mechanisms of alcohol-induced immunosuppression include defects in innate and adaptive immune responses. Monocytes and dendritic cells (DCs) link innate and adaptive immune responses as they recognize viral antigens and induce antigen-specific T-cell activation. We investigated the effects of alcohol on antigen-presenting cell functions. Acute alcohol consumption by healthy volunteers (vodka, 2 ml/kg) resulted in significantly reduced antigen-presenting cell function of monocyte-derived DCs. Reduced allostimulatory capacity of DCs treated with alcohol in vitro correlated with decreased co-stimulatory molecule (B7.1 and B7.2) expression, as well as with reduced interleukin (IL)-12 and increased IL-10 concentrations, in mixed lymphocyte cultures. Dendritic cells recognize viral antigens in hepatitis C virus (HCV) infection, and HCV disease is accelerated in alcohol-dependent individuals. For patients with chronic HCV infection, we found reduced allostimulatory capacity of myeloid DCs. Furthermore, DC function was reduced by in vitro alcohol treatment of DCs obtained from HCV-infected patients, supporting the suggestion that viral factors and alcohol may interact to doubly suppress DC functions. We found that induction of maturation with lipopolysaccharide could not fully ameliorate the reduced DC allostimulatory capacity caused by alcohol treatment, HCV infection, or their combination. In addition, soluble factors in the supernatants obtained from mixed lymphocyte cultures containing alcohol-treated DCs or DCs obtained from HCV-infected patients could transfer inhibition of T-cell proliferation in cultures containing DCs obtained from healthy volunteers. Anti–IL-10 neutralizing antibody ameliorated the reduced mixed lymphocyte reaction containing DCs obtained from HCV-infected patients, whereas exogenous IL-12, but not anti–IL-10, treatment ameliorated the reduced T-cell proliferation induced by alcohol treatment of DCs obtained from healthy volunteers. Our results support the suggestion that both acute alcohol intake and in vitro alcohol treatment inhibit DC antigen-presenting cell function and support the hypothesis that viral factors interact with alcohol to reduce DC functions in HCV infection.