Selective impairments in dendritic cell-associated function distinguish hepatitis C virus and HIV infection
Selective impairments in dendritic cell-associated function distinguish hepatitis C virus and HIV infection
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DOI：
10.4049/jimmunol.172.8.4907
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发表时间：
2004-04-15
影响因子：
4.4
通讯作者：
Valdez, H
中科院分区：
文献类型：
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作者：
Anthony, DD;Yonkers, NL;Valdez, H
APC功能受损可能在丙型肝炎病毒（HCV）和HIV感染的慢性化中起重要作用。为了研究HCV和HIV感染对未成熟树突状细胞（DC）的单独和联合作用，我们在健康对照组和慢性HCV、HIV和HCV-HIV感染者中，通过Toll样受体配体诱导的IFN-α和IL-12测定了骨髓源DC（MDC）和浆细胞源DC（PDC）的频率和功能。为了评估先天免疫和获得性免疫之间的关系，我们测量了HCV特异性IFN-γ产生T细胞的频率。MDC频率在HIV感染中倾向于降低（1.8倍），而PDC频率在HCV感染中最低限度地降低（1.4倍）。相比之下，在HIV感染的受试者中观察到非PDC相关的IFN-α产生显著减少（17倍），而在HCV感染的受试者中PDC相关的IFN-α产生显著减少（20倍）。HCV-HIV混合感染时，非PDC和PDC功能均受损。在HCV和HIV感染的受试者中，MDC相关的IL-12产生显著减少（超过10倍）。功能缺陷随着缓慢进展的HIV感染而减弱。与单纯感染HCV的受试者相比，HCV-HIV受试者中具有HCV特异性、T细胞反应的受试者比例以及识别的抗原数量减少。在HCV感染的受试者中，MDC相关的IL-12产生和HCV特异性T细胞频率之间存在正相关性。这些结果表明，未成熟DC功能在HIV和HCV感染中失调，但有差异，并且这些缺陷在缓慢进行的HIV感染中减弱。这些选择性不同的损害可能有助于降低适应性免疫反应，HCV和HIV的合并感染。
Impaired APC functions may play important roles in chronicity of hepatitis C virus (HCV) and HIV infections. To investigate the separate and combined effects of HCV and HIV infection on immature dendritic cells (DCs), we evaluated myeloid-derived DC (MDC) and plasmacytoid-derived DC (PDC) frequencies and functions, measured by Toll-like receptor ligand-induced IFN-alpha and IL-12, in healthy controls and subjects with chronic HCV, HIV, and HCV-HIV infection. To evaluate the relation between innate and adaptive immunity, we measured HCV-specific IFN-gamma-producing T cell frequency. MDC frequencies tended to be reduced in HIV infection (1.8-fold), while PDC frequencies were minimally reduced in HCV infection (1.4-fold). In contrast, a striking reduction in non-PDC-associated IFN-alpha production was observed in HIV-infected subjects (17-fold), while PDC-associated IFN-alpha production was markedly reduced in HCV-infected subjects (20-fold). Both non-PDC and PDC functions were impaired in HCV-HIV coinfection. MDC-associated IL-12 production was markedly reduced in both HCV and HIV-infected subjects (over 10-fold). Functional defects were attenuated with slowly progressive HIV infection. The proportion of subjects with HCV-specific, T cell responses, and the number of Ags recognized were reduced in HCV-HIV subjects as compared with HCV singly infected subjects. A positive association was observed between MDC-associated IL-12 production and HCV-specific T cell frequency in HCV-infected subjects. These results indicate that immature DC function is dysregulated in HIV and HCV infections, but differentially, and that these defects are attenuated in slowly progressive HIV infection. These selectively different impairments may contribute to the reduced adaptive immune response to HCV in HCV-HIV coinfection.