Human Immature Langerhans Cells Restrict CXCR4-using HIV-1 Transmission

Overview

Journal Retrovirology

Publisher Biomed Central

Specialty Microbiology

Date 2014 Jul 4

PMID 24990163

Citations 22

Authors

Ramin Sarrami-Forooshani

Annelies W Mesman

Nienke H van Teijlingen

Joris K Sprokholt

Michiel van der Vlist

Carla M S Ribeiro

Teunis B H Geijtenbeek

Affiliations

Soon will be listed here.

Abstract

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.

Citing Articles

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Immune activation of vaginal human Langerhans cells increases susceptibility to HIV-1 infection.

van Teijlingen N, Eder J, Sarrami-Forooshani R, Zijlstra-Willems E, Roovers J, van Leeuwen E Sci Rep. 2023; 13(1):3283.

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