Differential compartmentalization of HIV-targeting immune cells in inner and outer foreskin tissue.

Differential compartmentalization of HIV-targeting immune cells in inner and outer foreskin tissue.
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内包皮组织和外包皮组织中 HIV 靶向免疫细胞的差异区室化

DOI:
10.1371/journal.pone.0085176
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发表时间:
2014
期刊:
影响因子:
3.7
通讯作者:
Zhang X
Zhang X
中科院分区:
综合性期刊3区
文献类型:
--
作者:
Liu A;Yang Y;Liu L;Meng Z;Li L;Qiu C;Xu J;Zhang X

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离体包皮模型已经证明,内包皮比外包皮更容易感染HIV-1。在本研究中,我们的特点是划分的HIV-1靶细胞和量化这些细胞在表皮和真皮的内,外包皮使用免疫组织化学和流式细胞术。我们的数据表明,包皮内表皮比包皮外表皮更富含CD 4 + T细胞和朗格汉斯细胞(LC),并共同表达CCR 5和α4β7受体。有趣的是,绝大多数CD 4 + T细胞和LC表达CCR 5,但不表达CXCR 4,这表明内包皮可能更有效地捕获和传播R5嗜性HIV毒株。此外,淋巴聚集体,由T细胞,巨噬细胞和树突状细胞(DC)在真皮中,更接近上皮表面的内包皮比外包皮。由于树突状细胞能够捕获艾滋病毒颗粒并将其传递给易感靶细胞,因此艾滋病毒可能能够通过劫持该组织中增强的免疫通讯途径来更有效地感染内包皮。在包皮外植体培养模型中接种HIV-1颗粒后,内包皮上清液中p24抗原的水平略高于外包皮,尽管这种差异不显著。本研究首次使用CCR 5和α4β7来鉴定包皮中的HIV靶细胞。我们的数据表明,内包皮比外包皮更富含HIV靶免疫细胞,并且这种组织的结构是为了促进HIV传播和复制的免疫细胞之间的有效通信。此外,我们的数据表明,HIV性传播的R5向性可能是通过粘膜中HIV靶细胞上的固有受体组成形成的。
Ex vivo foreskin models have demonstrated that inner foreskin is more susceptible to HIV-1 infection than outer foreskin. In the present study we characterized the compartition of HIV-1 target cells and quantified these cells in the epidermis and dermis of inner and outer foreskins using immunohistochemistry and flow cytometry. Our data showed that the epidermis of the inner foreskin was more enriched with CD4+ T cells and Langerhans cells (LCs), with the co-expression of CCR5 and α4β7 receptors, than the outer foreskin. Interestingly, the vast majority of CD4+ T cells and LCs expressed CCR5, but not CXCR4, indicating that the inner foreskin might capture and transmit R5-tropic HIV strains more efficiently. In addition, lymphoid aggregates, composed of T cells, macrophages and dendritic cells (DCs) in the dermis, were closer to the epithelial surface in the inner foreskin than in the outer foreskin. As dendritic cells are able to capture and pass HIV particles to susceptible target cells, HIV may be able to more efficiently infect the inner foreskin by hijacking the augmented immune communication pathways in this tissue. After the inoculation of HIV-1 particles in a foreskin explant culture model, the level of p24 antigen in the supernatant from the inner foreskin was slightly higher than that from the outer foreskin, although this difference was not significant. The present study is the first to employ both CCR5 and α4β7 to identify HIV target cells in the foreskin. Our data demonstrated that the inner foreskin was more enriched with HIV target immune cells than the outer foreskin, and this tissue was structured for efficient communication among immune cells that may promote HIV transmission and replication. In addition, our data suggests the R5-tropism of HIV sexual transmission is likely shaped through the inherent receptor composition on HIV target cells in the mucosa.
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