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

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, Meritxell Genescà
• Journal: Frontiers in immunology (Front Immunol) Vol. 10 Pg. 825 ( 2019) ISSN: 1664-3224 [Electronic] Switzerland
• PMID: 31114569 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Interferon Type I
• SIGLEC1 protein, human
• Sialic Acid Binding Ig-like Lectin 1

Topics

• Adult
• Aged
• Aged, 80 and over
• Biological Transport, Active (immunology)
• Cervix Uteri (immunology, pathology, virology)
• Dendritic Cells (immunology, pathology, virology)
• Female
• HEK293 Cells
• HIV Infections (immunology, pathology)
• HIV-1 (physiology)
• Humans
• Interferon Type I (immunology)
• Middle Aged
• Mucous Membrane (immunology, pathology, virology)
• Sialic Acid Binding Ig-like Lectin 1 (immunology)
• Virus Replication (immunology)