Impact of chemokine C-C ligand 27, foreskin anatomy and sexually transmitted infections on HIV-1 target cell availability in adolescent South African males
Impact of chemokine C-C ligand 27, foreskin anatomy and sexually transmitted infections on HIV-1 target cell availability in adolescent South African males
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DOI：
10.1038/s41385-019-0209-6
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发表时间：
2020-01-01
影响因子：
8
通讯作者：
Hope, Thomas J.
中科院分区：
文献类型：
--
作者：
Gray, Clive M.;O'Hagan, Kyle L.;Hope, Thomas J.
我们比较了接受医学包皮环切术的青少年男性的外包皮和内包皮组织，以更好地了解增加包皮中HIV靶细胞可用性的信号。我们测量了趋化因子基因表达和性传播感染（STI）对T细胞和朗格汉斯细胞密度和位置的影响。趋化因子C-C配体27（CCL 27）在包皮内层中的表达是包皮外层的6.94倍。我们发现，无论STI状态如何，内包皮上皮中的CD 4（+）CCR 5（+）细胞密度/mm（2）较高，与CCL 27基因表达较高平行。在STI存在的情况下，外包皮和内包皮下层中的CD 4（+）CCR 5（+）细胞/mm 2细胞数量较高，同时两种组织中的CD 207（+）朗格汉斯细胞（LC）数量也较高，在STI存在的情况下，后者细胞更接近外FS的角蛋白表面。当我们测试外源性CCL 27诱导包皮组织中T细胞迁移的能力时，作为响应，CD 4 + T细胞能够重新定位到包皮内上皮。我们提供了新的见解CCL 27和性传播感染对免疫和HIV-1靶细胞的变化在包皮的影响。
We compared outer and inner foreskin tissue from adolescent males undergoing medical male circumcision to better understand signals that increase HIV target cell availability in the foreskin. We measured chemokine gene expression and the impact of sexually transmitted infections (STIs) on the density and location of T and Langerhans cells. Chemokine C-C ligand 27 (CCL27) was expressed 6.94-fold higher in the inner foreskin when compared with the outer foreskin. We show that the density of CD4(+)CCR5(+) cells/mm(2) was higher in the epithelium of the inner foreskin, regardless of STI status, in parallel with higher CCL27 gene expression. In the presence of STIs, there were higher numbers of CD4(+)CCR5(+) cells/mm(2) cells in the sub-stratum of the outer and inner foreskin with concurrently higher number of CD207(+) Langerhans cells (LC) in both tissues, with the latter cells being closer to the keratin surface of the outer FS in the presence of an STI. When we tested the ability of exogenous CCL27 to induce T-cell migration in foreskin tissue, CD4 + T cells were able to relocate to the inner foreskin epithelium in response. We provide novel insight into the impact CCL27 and STIs on immune and HIV-1 target cell changes in the foreskin.