Lymph node migratory dendritic cells modulate HIV-1 transcription through PD-1 engagement.
Anti-HIV Agents
/ therapeutic use
Antibodies, Monoclonal, Humanized
/ administration & dosage
Cell Movement
/ immunology
Cellular Microenvironment
/ immunology
Coculture Techniques
Dendritic Cells
/ immunology
Germinal Center
/ immunology
HIV Infections
/ drug therapy
HIV-1
/ genetics
Host Microbial Interactions
/ immunology
Humans
In Vitro Techniques
Lymph Nodes
/ immunology
Programmed Cell Death 1 Ligand 2 Protein
/ metabolism
Programmed Cell Death 1 Receptor
/ antagonists & inhibitors
Receptors, Immunologic
/ metabolism
Receptors, Virus
/ metabolism
T-Lymphocytes, Helper-Inducer
/ immunology
Transcription, Genetic
Virulence
Journal
PLoS pathogens
ISSN: 1553-7374
Titre abrégé: PLoS Pathog
Pays: United States
ID NLM: 101238921
Informations de publication
Date de publication:
07 2019
07 2019
Historique:
received:
15
03
2019
accepted:
14
06
2019
revised:
01
08
2019
pubmed:
23
7
2019
medline:
3
1
2020
entrez:
23
7
2019
Statut:
epublish
Résumé
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.
Identifiants
pubmed: 31329640
doi: 10.1371/journal.ppat.1007918
pii: PPATHOGENS-D-19-00505
pmc: PMC6675123
doi:
Substances chimiques
Anti-HIV Agents
0
Antibodies, Monoclonal, Humanized
0
PDCD1 protein, human
0
PDCD1LG2 protein, human
0
Programmed Cell Death 1 Ligand 2 Protein
0
Programmed Cell Death 1 Receptor
0
Receptors, Immunologic
0
Receptors, Virus
0
TIGIT protein, human
0
poliovirus receptor
0
pembrolizumab
DPT0O3T46P
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
e1007918Déclaration de conflit d'intérêts
The authors declare no competing interests.
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