Lymph node migratory dendritic cells modulate HIV-1 transcription through PD-1 engagement

Riddhima Banga; Caterina Rebecchini; Francesco Andrea Procopio; Alessandra Noto; Olivia Munoz; Kalliopi Ioannidou; Craig Fenwick; Khalid Ohmiti; Matthias Cavassini; Jean-Marc Corpataux; Laurence de Leval; Giuseppe Pantaleo; Matthieu Perreau

doi:10.1371/journal.ppat.1007918

Lymph node migratory dendritic cells modulate HIV-1 transcription through PD-1 engagement

PLoS Pathog. 2019 Jul 22;15(7):e1007918. doi: 10.1371/journal.ppat.1007918. eCollection 2019 Jul.

Affiliations

¹ Service of Immunology and Allergy, Lausanne University Hospital, University of Lausanne, Lausanne, Switzerland.
² Institute of Pathology, Lausanne University Hospital, University of Lausanne, Lausanne, Switzerland.
³ Service of Infectious Diseases, Lausanne University Hospital, University of Lausanne, Lausanne, Switzerland.
⁴ Service of Vascular Surgery, Lausanne University Hospital, University of Lausanne, Lausanne, Switzerland.
⁵ Swiss Vaccine Research Institute, Lausanne University Hospital, University of Lausanne, Lausanne, Switzerland.

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.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

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

Substances

Anti-HIV Agents
Antibodies, Monoclonal, Humanized
PDCD1 protein, human
PDCD1LG2 protein, human
Programmed Cell Death 1 Ligand 2 Protein
Programmed Cell Death 1 Receptor
Receptors, Immunologic
Receptors, Virus
TIGIT protein, human
poliovirus receptor
pembrolizumab

Grants and funding

This work was supported by Swiss National Science Foundation Grants 320030_173071 to M. Perreau and by an educational grant from FONDATION MACHAON to R. Banga. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.