TLR Agonists Enhance HIV-Specific T-Cell Response Mediated by Plasmacytoid Dendritic Cells in Diverse HIV-1 Disease Progression Phenotypes

Autor: Maria Reyes Jimenez-Leon, Carmen Gasca-Capote, Laura Tarancon-Diez, Beatriz Dominguez-Molina, Macarena Lopez-Verdugo, Ryan Ritraj, Ana Isabel Alvarez-Rios, Joana Vitallé, Sara Bachiller, Alberto Pérez-Gómez, Nuria Espinosa, Cristina Roca-Oporto, Mohamed Rafii-El-Idrissi Benhnia, Alicia Gutierrez-Valencia, Luis Fernando López-Cortés, Ezequiel Ruiz-Mateos
Rok vydání: 2022
Popis: Plasmacytoid dendritic cells (pDCs) sense microbial products through TLR-7 and -9 and translate this sensing in Interferon-α (IFN-α) production and T-cell polarization. The understanding of the mechanisms involved in pDCs stimulation may contribute to immunotherapeutic strategies aiming to decrease HIV-1 reservoir. Here, we characterize the immunomodulatory effects of TLR agonist stimulations through a pDC/T-cell coculture in different HIV-1 disease progression phenotypes and healthy donors (HD). pDCs were previously stimulated with AT-2-HIV-1, CpGA, CpGC and GS9620. After coculture with autologous CD4 or CD8 T-cells we observed an increase of pDCs activation markers levels, interferon related genes, HIV-1 restriction factors and cytokines levels. This pDCs coordinate activation was prominent with CpGC and GS9620 and induced an increase of HIV-specific T-cell response. These results shed light on the mechanisms associated with TLR-specific pDCs stimulation associated with T cell polarization for eliciting antiviral response which is essential for HIV eradication strategies.
Databáze: OpenAIRE