人类未成熟朗格汉斯细胞限制利用CXCR4的HIV-1传播。

Human immature Langerhans cells restrict CXCR4-using HIV-1 transmission.

作者信息

Sarrami-Forooshani Ramin, Mesman Annelies W, van Teijlingen Nienke H, Sprokholt Joris K, van der Vlist Michiel, Ribeiro Carla M S, Geijtenbeek Teunis B H

机构信息

Department of Experimental Immunology, Academic Medical Center, University of Amsterdam, Meibergdreef 9, 1105 AZ Amsterdam, The Netherlands.

出版信息

Retrovirology. 2014 Jul 2;11:52. doi: 10.1186/1742-4690-11-52.

BACKGROUND

Sexual transmission is the main route of HIV-1 infection and the CCR5-using (R5) HIV-1 is predominantly transmitted, even though CXCR4-using (X4) HIV-1 is often abundant in chronic HIV-1 patients. The mechanisms underlying this tropism selection are unclear. Mucosal Langerhans cells (LCs) are the first immune cells to encounter HIV-1 and here we investigated the role of LCs in selection of R5 HIV-1 using an ex vivo epidermal and vaginal transmission models.

RESULTS

Immature LCs were productively infected by X4 as well as R5 HIV-1. However, only R5 but not X4 viruses were selectively transmitted by immature LCs to T cells. Transmission of HIV-1 was depended on de novo production of HIV-1 in LCs, since it could be inhibited by CCR5 fusion inhibitors as well as reverse transcription inhibitors. Notably, the activation state of LCs affected the restriction in X4 HIV-1 transmission; immune activation by TNF facilitated transmission of X4 as well as R5 HIV-1.

CONCLUSIONS

These data suggest that LCs play a crucial role in R5 selection and that immature LCs effectively restrict X4 at the level of transmission.

背景

性传播是HIV-1感染的主要途径，尽管在慢性HIV-1患者中使用CXCR4的（X4）HIV-1通常大量存在，但主要传播的是使用CCR5的（R5）HIV-1。这种嗜性选择的潜在机制尚不清楚。黏膜朗格汉斯细胞（LCs）是最早接触HIV-1的免疫细胞，在此我们使用体外表皮和阴道传播模型研究了LCs在R5 HIV-1选择中的作用。

结果

未成熟的LCs能被X4和R5 HIV-1有效感染。然而，只有R5而非X4病毒能被未成熟的LCs选择性地传播给T细胞。HIV-1的传播依赖于LCs中HIV-1的从头产生，因为它可被CCR5融合抑制剂以及逆转录抑制剂抑制。值得注意的是，LCs的激活状态影响X4 HIV-1传播的限制；TNF介导的免疫激活促进了X4和R5 HIV-1的传播。