Dendritic cells from the cervical mucosa capture and transfer HIV-1 via Siglec-1

Dendritic cells from the cervical mucosa capture and transfer HIV-1 via Siglec-1

Online publication: 30/04/2019 Journal: Frontiers in Immunology

Abstract:

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.

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

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