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

Retrovirology

Teunis BH Geijtenbeek²  Carla MS Ribeiro²  Michiel van der Vlist¹  Joris K Sprokholt²  Nienke H van Teijlingen²  Annelies W Mesman²  Ramin Sarrami-Forooshani² 

[1] Immune Regulation, Laboratory of Translational Immunology, University Medical Center Utrecht, Postbus 85500, 3508 GA Utrecht, The Netherlands;Department of Experimental Immunology, Academic Medical Center, University of Amsterdam, Meibergdreef 9, 1105 AZ Amsterdam, The Netherlands

关键词: Transmission;    Infection;    ex vivo model;    Langerhans cells;    Selection of R5;    CCR5-using HIV-1 (R5);    CXCR4-using HIV-1 (X4);    Coreceptor usage;    Tropism;    HIV-1;   

Others  :  1131844
DOI  :  10.1186/1742-4690-11-52

 received in 2013-12-20, accepted in 2014-06-12,  发布年份 2014

【 摘 要 】

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.

【 授权许可】

   
2014 Sarrami-Forooshani et al.; licensee BioMed Central Ltd.

【 图 表 】

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