Centre for Virus Research, The Westmead Institute for Medical Research, 176 Hawkesbury Road, Westmead, New South Wales, 2145, Australia.
The University of Sydney, Sydney, 2006, New South Wales, Australia.
Nat Commun. 2019 Jun 21;10(1):2759. doi: 10.1038/s41467-019-10697-w.
Langerhans cells (LC) are thought to be the only mononuclear phagocyte population in the epidermis where they detect pathogens. Here, we show that CD11c dendritic cells (DCs) are also present. These cells are transcriptionally similar to dermal cDC2 but are more efficient antigen-presenting cells. Compared to LCs, epidermal CD11c DCs are enriched in anogenital tissues where they preferentially interact with HIV, express the higher levels of HIV entry receptor CCR5, support the higher levels of HIV uptake and replication and are more efficient at transmitting the virus to CD4 T cells. Importantly, these findings are observed using both a lab-adapted and transmitted/founder strain of HIV. We also describe a CD33 cell population, which is transcriptionally similar to LCs but does not appear to function as antigen-presenting cells or acts as HIV target cells. Our findings reveal that epidermal DCs in anogenital tissues potentially play a key role in sexual transmission of HIV.
朗格汉斯细胞（LC）被认为是表皮中唯一的单核吞噬细胞群，可在表皮中检测病原体。在这里，我们发现 CD11c 树突状细胞（DC）也存在。这些细胞在转录上与真皮 cDC2 相似，但作为抗原呈递细胞的效率更高。与 LC 相比，表皮 CD11c DC 在肛门生殖器组织中更为丰富，它们优先与 HIV 相互作用，表达更高水平的 HIV 进入受体 CCR5，支持更高水平的 HIV 摄取和复制，并且更有效地将病毒传播给 CD4 T 细胞。重要的是，这些发现使用实验室适应和传播/原始株 HIV 均可观察到。我们还描述了一种 CD33 细胞群，该细胞群在转录上与 LC 相似，但似乎不作为抗原呈递细胞或作为 HIV 靶细胞发挥作用。我们的研究结果表明，肛门生殖器组织中的表皮 DC 可能在 HIV 的性传播中发挥关键作用。
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