Thumann C, Schvoerer E, Abraham J-D, Bohbot A, Stoll-Keller F, Aubertin A-M, Kieny M-P
Inserm U748, institut de virologie, université Louis-Pasteur, 3, rue Koeberlé, 67000 Strasbourg, France.
Gastroenterol Clin Biol. 2008 Jan;32(1 Pt. 1):59-68. doi: 10.1016/j.gcb.2007.12.006. Epub 2008 Mar 4.
Infection with hepatitis C virus (HCV) results in chronic hepatitis in more than 70% of cases. Alterations in the maturation of dendritic cells (DC) might play a role in the immune system's inability to eliminate the virus, although viral factors that could be involved have not been identified. This study in vitro investigated whether HCV structural proteins affect maturation of monocyte-derived DC.
HCV proteins (core, E1, E2) were expressed by transduction with recombinant adenoviruses of immature DC. The ability of these transduced DC to respond to a maturation stimulus was evaluated by measuring cell surface markers, allogenic lymphocyte stimulation and interleukin (IL)-12 production.
Expression of HCV structural proteins did not modify DC maturation in the presence of lipopolysaccharide, as determined by their phenotype and stimulatory functioning. IL-12 secretion was not affected by HCV protein expression in mature DC.
Our results suggest that HCV structural proteins do not affect maturation of monocyte-derived DC by lipopolysaccharide. These findings are important for further studies to clarify the pathogenesis of chronic HCV infection and towards the rational design of cellular vaccine approaches for immunotherapy against hepatitis C.
丙型肝炎病毒（HCV）感染在超过70%的病例中会导致慢性肝炎。树突状细胞（DC）成熟过程的改变可能在免疫系统无法清除病毒中起作用，尽管尚未确定可能涉及的病毒因素。本体外研究调查了HCV结构蛋白是否影响单核细胞来源的DC的成熟。
通过用未成熟DC的重组腺病毒转导来表达HCV蛋白（核心蛋白、E1蛋白、E2蛋白）。通过测量细胞表面标志物、异体淋巴细胞刺激和白细胞介素（IL）-12的产生来评估这些转导的DC对成熟刺激的反应能力。
根据其表型和刺激功能确定，在存在脂多糖的情况下，HCV结构蛋白的表达并未改变DC的成熟。成熟DC中IL-12的分泌不受HCV蛋白表达的影响。
我们的结果表明，HCV结构蛋白不会通过脂多糖影响单核细胞来源的DC的成熟。这些发现对于进一步阐明慢性HCV感染的发病机制以及合理设计用于丙型肝炎免疫治疗的细胞疫苗方法具有重要意义。
