Lymph node migratory dendritic cells modulate HIV-1 transcription through PD-1 engagement.
Details
Serval ID
serval:BIB_1FF4BBBC8958
Type
Article: article from journal or magazin.
Collection
Publications
Institution
Title
Lymph node migratory dendritic cells modulate HIV-1 transcription through PD-1 engagement.
Journal
PLoS pathogens
ISSN
1553-7374 (Electronic)
ISSN-L
1553-7366
Publication state
Published
Issued date
07/2019
Peer-reviewed
Oui
Volume
15
Number
7
Pages
e1007918
Language
english
Notes
Publication types: Journal Article ; Research Support, Non-U.S. Gov't
Publication Status: epublish
Publication Status: epublish
Abstract
T-follicular helper (Tfh) cells, co-expressing PD-1 and TIGIT, serve as a major cell reservoir for HIV-1 and are responsible for active and persistent HIV-1 transcription after prolonged antiretroviral therapy (ART). However, the precise mechanisms regulating HIV-1 transcription in lymph nodes (LNs) remain unclear. In the present study, we investigated the potential role of immune checkpoint (IC)/IC-Ligand (IC-L) interactions on HIV-1 transcription in LN-microenvironment. We show that PD-L1 (PD-1-ligand) and CD155 (TIGIT-ligand) are predominantly co-expressed on LN migratory (CD1chighCCR7+CD127+) dendritic cells (DCs), that locate predominantly in extra-follicular areas in ART treated individuals. We demonstrate that TCR-mediated HIV production is suppressed in vitro in the presence of recombinant PD-L1 or CD155 and, more importantly, when LN migratory DCs are co-cultured with PD-1+/Tfh cells. These results indicate that LN migratory DCs expressing IC-Ls may more efficiently restrict HIV-1 transcription in the extra-follicular areas and explain the persistence of HIV transcription in PD-1+/Tfh cells after prolonged ART within germinal centers.
Keywords
Anti-HIV Agents/therapeutic use, Antibodies, Monoclonal, Humanized/administration & dosage, Cell Movement/immunology, Cellular Microenvironment/immunology, Coculture Techniques, Dendritic Cells/immunology, Dendritic Cells/virology, Germinal Center/immunology, Germinal Center/virology, HIV Infections/drug therapy, HIV Infections/immunology, HIV Infections/virology, HIV-1/genetics, HIV-1/immunology, HIV-1/pathogenicity, Host Microbial Interactions/immunology, Humans, In Vitro Techniques, Lymph Nodes/immunology, Lymph Nodes/virology, Programmed Cell Death 1 Ligand 2 Protein/metabolism, Programmed Cell Death 1 Receptor/antagonists & inhibitors, Programmed Cell Death 1 Receptor/metabolism, Receptors, Immunologic/metabolism, Receptors, Virus/metabolism, T-Lymphocytes, Helper-Inducer/immunology, T-Lymphocytes, Helper-Inducer/virology, Transcription, Genetic, Virulence
Pubmed
Web of science
Open Access
Yes
Create date
23/07/2019 11:46
Last modification date
27/08/2024 9:18