Frontiers in Immunology (Apr 2019)

Dendritic Cells From the Cervical Mucosa Capture and Transfer HIV-1 via Siglec-1

  • Daniel Perez-Zsolt,
  • Daniel Perez-Zsolt,
  • Jon Cantero-Pérez,
  • Jon Cantero-Pérez,
  • Itziar Erkizia,
  • Susana Benet,
  • Susana Benet,
  • Maria Pino,
  • Carla Serra-Peinado,
  • Alba Hernández-Gallego,
  • Alba Hernández-Gallego,
  • Josep Castellví,
  • Josep Castellví,
  • Gustavo Tapia,
  • Gustavo Tapia,
  • Gustavo Tapia,
  • Vicent Arnau-Saz,
  • Vicent Arnau-Saz,
  • Julio Garrido,
  • Antoni Tarrats,
  • Maria J. Buzón,
  • Javier Martinez-Picado,
  • Javier Martinez-Picado,
  • Javier Martinez-Picado,
  • Nuria Izquierdo-Useros,
  • Nuria Izquierdo-Useros,
  • Meritxell Genescà,
  • Meritxell Genescà

DOI
https://doi.org/10.3389/fimmu.2019.00825
Journal volume & issue
Vol. 10

Abstract

Read online

Antigen presenting cells from the cervical mucosa are thought to amplify incoming HIV-1 and spread infection systemically without being productively infected. Yet, the molecular mechanism at the cervical mucosa underlying this viral transmission pathway remains unknown. Here we identified a subset of HLA-DR+ CD14+ CD11c+ cervical DCs at the lamina propria of the ectocervix and the endocervix that expressed the type-I interferon inducible lectin Siglec-1 (CD169), which promoted viral uptake. In the cervical biopsy of a viremic HIV-1+ patient, Siglec-1+ cells harbored HIV-1-containing compartments, demonstrating that in vivo, these cells trap viruses. Ex vivo, a type-I interferon antiviral environment enhanced viral capture and trans-infection via Siglec-1. Nonetheless, HIV-1 transfer via cervical DCs was effectively prevented with antibodies against Siglec-1. Our findings contribute to decipher how cervical DCs may boost HIV-1 replication and promote systemic viral spread from the cervical mucosa, and highlight the importance of including inhibitors against Siglec-1 in microbicidal strategies.

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