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 <i>in vivo</i>, these cells trap viruses<i>. Ex vivo</i>, a type-I interferon antiviral environment enhanced viral capture and <i>trans</i>-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.