TY - JOUR
T1 - Dendritic Cells From the Cervical Mucosa Capture and Transfer HIV-1 via Siglec-1
AU - Perez-Zsolt, Daniel
AU - Cantero-Pérez, Jon
AU - Erkizia, Itziar
AU - Benet, Susana
AU - Pino, Maria
AU - Serra-Peinado, Carla
AU - Hernández-Gallego, Alba
AU - Castellví, Josep
AU - Tapia, Gustavo
AU - Arnau-Saz, Vicent
AU - Garrido, Julio
AU - Tarrats, Antoni
AU - Buzón, Maria J.
AU - Martinez-Picado, Javier
AU - Izquierdo-Useros, Nuria
AU - Genescà, Meritxell
PY - 2019/1/1
Y1 - 2019/1/1
N2 - 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.
AB - 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.
KW - HIV-1
KW - Siglec-1
KW - cervix
KW - myeloid cells
KW - trans-infection
U2 - 10.3389/fimmu.2019.00825
DO - 10.3389/fimmu.2019.00825
M3 - Article
C2 - 31114569
SN - 1664-3224
VL - 10
SP - 825
JO - Frontiers in immunology
JF - Frontiers in immunology
ER -
