Titre :

Activation of Nod2 signaling upon Norovirus infection enhances antiviral immunity and susceptibility to colitis

Auteur(s) :

Muharram, Ghaffar [Auteur correspondant]
Centre d’Infection et d’Immunité de Lille - INSERM U 1019 - UMR 9017 - UMR 8204 [CIIL]
Thépaut, Marion [Auteur]
Centre d’Infection et d’Immunité de Lille - INSERM U 1019 - UMR 9017 - UMR 8204 [CIIL]
Lobert, Pierre-Emmanuel [Auteur]
Laboratoire de Virologie - ULR 3610 [Laboratoire de Virologie]
Grandjean, Teddy [Auteur]
Centre d’Infection et d’Immunité de Lille - INSERM U 1019 - UMR 9017 - UMR 8204 [CIIL]
Boulard, Olivier [Auteur]
Laboratoire de Physiologie Cellulaire - U 1003 [PHYCELL]
Delacre, Myriam [Auteur]
Centre d’Infection et d’Immunité de Lille - INSERM U 1019 - UMR 9017 - UMR 8204 [CIIL]
Wakeford, Emmrich [Auteur]
Centre d’Infection et d’Immunité de Lille - INSERM U 1019 - UMR 9017 - UMR 8204 [CIIL]
Wheeler, Richard [Auteur]
Biologie et Génétique de la Paroi bactérienne - Biology and Genetics of Bacterial Cell Wall
Poulin, Lionel [Auteur]
Laboratoire de Physiologie Cellulaire - U 1003 [PHYCELL]
Gomperts Boneca, Ivo [Auteur]
Biologie et Génétique de la Paroi bactérienne - Biology and Genetics of Bacterial Cell Wall
Lafont, Frank [Auteur]
Centre d’Infection et d’Immunité de Lille - INSERM U 1019 - UMR 9017 - UMR 8204 [CIIL]
Michallet, Marie-Cécile [Auteur]
Centre de Recherche en Cancérologie de Lyon [UNICANCER/CRCL]
Hober, Didier [Auteur]
Laboratoire de Virologie - ULR 3610 [Laboratoire de Virologie]
Cadwell, Ken [Auteur]
New York University School of Medicine [NYU Grossman School of Medicine]
Chamaillard, Mathias [Auteur correspondant]
Laboratoire de Physiologie Cellulaire - U 1003 [PHYCELL]

Titre de la revue :

Gut Microbes

Éditeur :

Taylor & Francis

Date de publication :

2023-12-31

ISSN :

1949-0976

Mot(s)-clé(s) en anglais :

NOD2
Norovirus
Inflammation
Colitis
Macrophages
Signalling

Discipline(s) HAL :

Sciences du Vivant [q-bio]/Médecine humaine et pathologie/Maladies infectieuses
Sciences du Vivant [q-bio]/Immunologie/Immunité adaptative
Sciences du Vivant [q-bio]/Immunologie/Immunité innée
Sciences du Vivant [q-bio]/Médecine humaine et pathologie/Hépatologie et Gastroentérologie
Sciences du Vivant [q-bio]/Microbiologie et Parasitologie/Virologie

Résumé en anglais : [en]

Over 90% of epidemic nonbacterial gastroenteritis are caused by human Noroviruses (NoV) which are persisting in a substantial subset of people allowing their spread worldwide. It leads to a significant number of endemic ...
Lire la suite >Over 90% of epidemic nonbacterial gastroenteritis are caused by human Noroviruses (NoV) which are persisting in a substantial subset of people allowing their spread worldwide. It leads to a significant number of endemic cases and up to 70,000 children deaths in developing countries. NoVs are primarily transmitted through the fecal-oral route. To date studies have focused on the influence of the gut microbiota on enteric viral clearance by mucosal immunity. In this study, the use of mouse norovirus S99 (MNoV_S99) and CR6 (MNoV_CR6), two persistent strains, allowed us to provide evidence that the norovirus-induced exacerbation of colitis severity relied on bacterial sensing by nucleotide-binding oligomerization domain 2 (Nod2). Consequently, Nod2-deficient mice showed reduced levels of gravity of Dextran sodium sulphate (DSS)-induced colitis with both viral strains. And MNoV_CR6 viremia was heightened in Nod2-/- mice in comparison with animals hypomorphic for Atg16l1, that are prone to aggravated inflammation under DSS. Accordingly, the infection of macrophages derived from WT mice promoted the phosphorylation of Signal Transducer and Activator of Transcription1 (STAT1) and NOD2’s expression levels. Higher secretion of Tumor Necrosis Factor alpha (TNF) following NOD2 activation and better viral clearance were measured in these cells. By contrast, reduced levels of pSTAT1 and blunted downstream secretion of TNF were found in Nod2-deficient macrophages infected by MNoV_S99. Hence, our results uncover a previously unidentified virus-host-bacterial interplay that may represent a novel therapeutic target for treating noroviral origin gastroenteritis that may be linked with susceptibility to several common illnesses such as Crohn’s disease.Lire moins >

Langue :

Anglais

Comité de lecture :

Oui

Audience :

Internationale

Vulgarisation :

Non

Projet ANR :

Integrative Biology of Emerging Infectious Diseases
LUMIERE
Modulation de l'activité du cerveau par le peptidoglycan bactérien
Développment d'une infrastructure française distribuée coordonnée

Collections :

• Centre d'Infection et d'Immunité de Lille (CIIL) - U1019 - UMR 9017

Source :

Harvested from HAL