title: Human immature Langerhans cells restrict CXCR4-using HIV-1 transmission.
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.
authors.forename: Ramin
authors.initials: R
authors.lastname: Sarrami-Forooshani
authors.forename: Annelies W
authors.initials: AW
authors.lastname: Mesman
authors.forename: Nienke H
authors.initials: NH
authors.lastname: van Teijlingen
authors.forename: Joris K
authors.initials: JK
authors.lastname: Sprokholt
authors.forename: Michiel
authors.initials: M
authors.lastname: van der Vlist
authors.forename: Carla M S
authors.initials: CM
authors.lastname: Ribeiro
authors.affiliation: Department of Experimental Immunology, Academic Medical Center, University of Amsterdam, Meibergdreef 9, 1105 AZ Amsterdam, The Netherlands. t.b.geijtenbeek@amc.uva.nl.
authors.forename: Teunis B H
authors.initials: TB
authors.lastname: Geijtenbeek
mesh_terms: D015658:HIV Infections / Q000635:transmission*; D015497:HIV-1 / Q000502:physiology*; D006801:Humans; D007801:Langerhans Cells / Q000502:physiology* / Q000821:virology; D019718:Receptors, CXCR4 / Q000378:metabolism / Q000502:physiology*; D014409:Tumor Necrosis Factor-alpha / Q000494:pharmacology; D014779:Virus Replication
chemical_list: C527276:CXCR4 protein, human; D019718:Receptors, CXCR4; D014409:Tumor Necrosis Factor-alpha