NOD2 dependent signalling exacerbates the intestinal epithelium injury and limits murine Norovirus propagation
Résumé
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.
Fichier principal
MNoV Nod2_ revised manuscript with modifications overligned.pdf (360.45 Ko)
Télécharger le fichier
Figure 1_v211222.pdf (2.29 Mo)
Télécharger le fichier
Figure 2_v211222.pdf (2.16 Mo)
Télécharger le fichier
Figure 3_v211222.pdf (2.37 Mo)
Télécharger le fichier
Figure 4_v211222.pdf (77.14 Ko)
Télécharger le fichier
Figure S1_v211222.pdf (415.14 Ko)
Télécharger le fichier
Figure S2_v211222.pdf (101.08 Ko)
Télécharger le fichier
Origine : Fichiers produits par l'(les) auteur(s)
Commentaire : A new modified version as been deposited. This version was not been accepted by Gut Microbes.
Commentaire : A new modified version as been deposited. This version was not been accepted by Gut Microbes.