NOD2 dependent signalling exacerbates the ...
Document type :
Pré-publication ou Document de travail
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Title :
NOD2 dependent signalling exacerbates the intestinal epithelium injury and limits murine Norovirus propagation
Author(s) :
Muharram, Ghaffar [Auteur]
Centre d'Infection et d'Immunité de Lille (CIIL) - U1019 - UMR 9017
Thépaut, Marion [Auteur]
Institut de Génétique et Développement de Rennes [IGDR]
Lobert, Pierre-Emmanuel [Auteur]
Pathogenèse virale du diabète de type 1 - ULR 3610
Grandjean, Teddy [Auteur]
Centre d'Infection et d'Immunité de Lille (CIIL) - U1019 - UMR 9017
Boulard, Olivier [Auteur]
Physiologie Cellulaire (PHYCELL) - U1003
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 (CIIL) - U1019 - UMR 9017
Wheeler, Richard [Auteur]
Biologie et Génétique de la Paroi bactérienne - Biology and Genetics of Bacterial Cell Wall [BGPB]
POULIN, Lionel [Auteur]
Physiologie Cellulaire (PHYCELL) - U1003
Gomperts Boneca, Ivo [Auteur]
Biologie et Génétique de la Paroi bactérienne - Biology and Genetics of Bacterial Cell Wall [BGPB]
Lafont, Frank [Auteur]
Centre d'Infection et d'Immunité de Lille (CIIL) - U1019 - UMR 9017
Michallet, Marie-Cécile [Auteur]
Hober, Didier [Auteur]
Pathogenèse virale du diabète de type 1 - ULR 3610
Cadwell, Ken [Auteur]
New York University School of Medicine
Skirball Institute of Biomolecular Medicine
New York University Langone Medical Center [NYU Langone Medical Center]
Chamaillard, Mathias [Auteur]
Physiologie Cellulaire (PHYCELL) - U1003

Centre d'Infection et d'Immunité de Lille (CIIL) - U1019 - UMR 9017
Thépaut, Marion [Auteur]
Institut de Génétique et Développement de Rennes [IGDR]
Lobert, Pierre-Emmanuel [Auteur]

Pathogenèse virale du diabète de type 1 - ULR 3610
Grandjean, Teddy [Auteur]

Centre d'Infection et d'Immunité de Lille (CIIL) - U1019 - UMR 9017
Boulard, Olivier [Auteur]

Physiologie Cellulaire (PHYCELL) - U1003
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 (CIIL) - U1019 - UMR 9017
Wheeler, Richard [Auteur]
Biologie et Génétique de la Paroi bactérienne - Biology and Genetics of Bacterial Cell Wall [BGPB]
POULIN, Lionel [Auteur]
Physiologie Cellulaire (PHYCELL) - U1003
Gomperts Boneca, Ivo [Auteur]
Biologie et Génétique de la Paroi bactérienne - Biology and Genetics of Bacterial Cell Wall [BGPB]
Lafont, Frank [Auteur]

Centre d'Infection et d'Immunité de Lille (CIIL) - U1019 - UMR 9017
Michallet, Marie-Cécile [Auteur]
Hober, Didier [Auteur]

Pathogenèse virale du diabète de type 1 - ULR 3610
Cadwell, Ken [Auteur]
New York University School of Medicine
Skirball Institute of Biomolecular Medicine
New York University Langone Medical Center [NYU Langone Medical Center]
Chamaillard, Mathias [Auteur]

Physiologie Cellulaire (PHYCELL) - U1003
Production date :
2022-10
English keyword(s) :
NOD2
Norovirus
Inflammation
Colitis
Macrophages
Signalling
Norovirus
Inflammation
Colitis
Macrophages
Signalling
HAL domain(s) :
Sciences du Vivant [q-bio]
English abstract : [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 ...
Show more >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 death in developing countries. NoVs are primarily transmitted through the fecal-oral route. Studies to date have focused on the influence of the gut microbiota on their clearance by enteric immunity. In this study, the use of the persistent mouse Norovirus S99 strain (MNoV_S99) allowed us to provide evidence that bacterial sensing by nucleotide-binding oligomerization domain 2 (Nod2) promotes the noroviral associated pro-inflammatory pathology in a dextran sodium sulphate induced colitis mouse model. By contrast, the establishment of the pathology in the colon is improved in the absence of Nod2. We also show in our cellular models a greater phosphorylation of Signal Transducer and Activator of Transcription1 (STAT1) in macrophages infected by MNoV_S99 when compared with mock-infected cells. This increased STAT1 phosphorylation is associated with an induction of NOD2 expression in macrophages. This in turn enhances myeloid cells response to muramyl dipeptide (MDP) resulting into downstream pro-inflammatory cytokine secretion. Hence, our results uncover a previously unidentified virus-host-bacterial interplay that is particularly important for protecting against several common illnesses, such as Crohn’s disease.Show less >
Show more >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 death in developing countries. NoVs are primarily transmitted through the fecal-oral route. Studies to date have focused on the influence of the gut microbiota on their clearance by enteric immunity. In this study, the use of the persistent mouse Norovirus S99 strain (MNoV_S99) allowed us to provide evidence that bacterial sensing by nucleotide-binding oligomerization domain 2 (Nod2) promotes the noroviral associated pro-inflammatory pathology in a dextran sodium sulphate induced colitis mouse model. By contrast, the establishment of the pathology in the colon is improved in the absence of Nod2. We also show in our cellular models a greater phosphorylation of Signal Transducer and Activator of Transcription1 (STAT1) in macrophages infected by MNoV_S99 when compared with mock-infected cells. This increased STAT1 phosphorylation is associated with an induction of NOD2 expression in macrophages. This in turn enhances myeloid cells response to muramyl dipeptide (MDP) resulting into downstream pro-inflammatory cytokine secretion. Hence, our results uncover a previously unidentified virus-host-bacterial interplay that is particularly important for protecting against several common illnesses, such as Crohn’s disease.Show less >
Language :
Anglais
Collections :
Submission date :
2022-10-09T14:47:05Z
2022-10-27T09:17:56Z
2022-12-13T16:54:45Z
2023-01-04T14:42:03Z
2022-10-27T09:17:56Z
2022-12-13T16:54:45Z
2023-01-04T14:42:03Z
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