Title :

The Autophagy Nucleation Factor ATG9 Forms Nanoclusters with the HIV-1 Receptor DC-SIGN and Regulates Early Antiviral Autophagy in Human Dendritic Cells

Author(s) :

Papin, Laure [Auteur]
Lehmann, Martin [Auteur]
Lagisquet, Justine [Auteur]
Maarifi, Ghizlane [Auteur]
Robert-Hebmann, Véronique [Auteur]
Mariller, Christophe [Auteur]
Unité de Glycobiologie Structurale et Fonctionnelle (UGSF) - UMR 8576
Guerardel, Yann [Auteur]
Unité de Glycobiologie Structurale et Fonctionnelle (UGSF) - UMR 8576
Espert, Lucile [Auteur]
Haucke, Volker [Auteur]
Blanchet, Fabien P. [Auteur]

Journal title :

International Journal of Molecular Sciences

Abbreviated title :

IJMS

Volume number :

24

Pages :

9008

Publisher :

MDPI AG

Publication date :

2023-05-19

ISSN :

1422-0067

English keyword(s) :

autophagy
dendritic cells
HIV-1
DC-SIGN
innate immunity

HAL domain(s) :

Sciences du Vivant [q-bio]
Sciences du Vivant [q-bio]/Médecine humaine et pathologie/Maladies infectieuses
Sciences du Vivant [q-bio]/Immunologie/Immunité innée
Sciences du Vivant [q-bio]/Microbiologie et Parasitologie/Virologie
Chimie/Chimie théorique et/ou physique

English abstract : [en]

Dendritic cells (DC) are critical cellular mediators of host immunity, notably by expressing a broad panel of pattern recognition receptors. One of those receptors, the C-type lectin receptor DC-SIGN, was previously reported ...
Show more >Dendritic cells (DC) are critical cellular mediators of host immunity, notably by expressing a broad panel of pattern recognition receptors. One of those receptors, the C-type lectin receptor DC-SIGN, was previously reported as a regulator of endo/lysosomal targeting through functional connections with the autophagy pathway. Here, we confirmed that DC-SIGN internalization intersects with LC3+ autophagy structures in primary human monocyte-derived dendritic cells (MoDC). DC-SIGN engagement promoted autophagy flux which coincided with the recruitment of ATG-related factors. As such, the autophagy initiation factor ATG9 was found to be associated with DC-SIGN very early upon receptor engagement and required for an optimal DC-SIGN-mediated autophagy flux. The autophagy flux activation upon DC-SIGN engagement was recapitulated using engineered DC-SIGN-expressing epithelial cells in which ATG9 association with the receptor was also confirmed. Finally, Stimulated emission depletion (STED) microscopy performed in primary human MoDC revealed DC-SIGN-dependent submembrane nanoclusters formed with ATG9, which was required to degrade incoming viruses and further limit DC-mediated transmission of HIV-1 infection to CD4+ T lymphocytes. Our study unveils a physical association between the Pattern Recognition Receptor DC-SIGN and essential components of the autophagy pathway contributing to early endocytic events and the host’s antiviral immune response.Show less >

Language :

Anglais

Peer reviewed article :

Oui

Audience :

Internationale

Popular science :

Non

ANR Project :

Le catabolisme de la paroi mycobactérienne: vers le développement de nouveaux inhibiteurs

Administrative institution(s) :

Université de Lille
CNRS

Collections :

• Unité de Glycobiologie Structurale et Fonctionnelle (UGSF) - UMR 8576

Research team(s) :

Chemical Glycobiology

Submission date :

2023-11-08T10:51:12Z
2023-11-09T18:16:57Z
2023-11-10T14:43:53Z