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Efficient inhibition of HIV-1 replication in human immature monocyte-derived dendritic cells by purified anti–HIV-1 IgG without induction of maturation

机译:纯化的抗HIV-1 IgG有效抑制人未成熟单核细胞源性树突状细胞中HIV-1复制,而不会诱导成熟

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摘要

During mucosal HIV transmission, immature dendritic cells (DCs) present in the mucosa are among the first cellular targets of the virus. Previous studies have analyzed the inhibition of HIV-1 transfer from human mature DCs to T lymphocytes by neutralizing IgG, but so far no in vitro data regarding the capacity of antibodies to inhibit HIV-1 infection of immature DCs have been reported. Here, we found an increased HIV-inhibitory activity of monoclonal IgG and purified polyclonal IgG when immature monocyte-derived dendritic cells (iMDDCs) were used as target cells instead of autologous blood lymphocytes. We showed that FcγRII is involved in the mechanism for inhibiting HIV-1 infection of iMDDCs by IgG, whereas no induction of maturation was detected at concentrations of IgG that result in a 90% reduction of HIV replication. After induction of FcγRI expression on iMDDCs by IFN-γ, an augmentation of the HIV-inhibitory activity of IgG, related to the expression of FcγRI, was observed. Taken together, our results demonstrate the participation of FcγRs in HIV-1 inhibition by IgG when iMDDCs are the targets. We propose that IgG is able to efficiently inhibit HIV-1 replication in iMDDCs and should be one of the components to be induced by vaccination.
机译:在粘膜HIV传播过程中,粘膜中存在的未成熟树突状细胞(DC)是该病毒的第一个细胞靶标。先前的研究已经分析了通过中和IgG对HIV-1从人成熟DC转移到T淋巴细胞的抑制作用,但是到目前为止,还没有关于抗体抑制未成熟DC的HIV-1感染能力的体外数据。在这里,我们发现当未成熟单核细胞衍生的树突状细胞(iMDDCs)用作靶细胞而非自体血淋巴细胞时,单克隆IgG和纯化的多克隆IgG的HIV抑制活性增加。我们表明,FcγRII参与了抑制IgG抑制iMDDC的HIV-1感染的机制,而在IgG浓度下未检测到成熟诱导,导致HIV复制减少了90%。在IFN-γ诱导iMDDCs上的FcγRI表达后,观察到与FcγRI表达有关的IgG的HIV抑制活性增加。两者合计,我们的结果表明,当以iMDDC为靶标时,FcγR参与IgG对HIV-1的抑制。我们建议IgG能够有效地抑制iMDDCs中的HIV-1复制,并且应该是通过疫苗诱导的成分之一。

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