Le rôle du récepteur NOD2 : un régulateur de l'infection virale et de la réponse inflammatoire

Authors: Egarnes, Benoit
Advisor: Gosselin, Jean
Abstract: Three major classes of innate immunity receptors are known to be involved in pathogen recognition: the Toll-like receptors (TLRs), the Retinoic acid-inducible gene I-like receptors (RLRs), and the Nucleotide-binding oligomerization domain-like receptors (NLRs). NOD2, a member of the NLR family, was initially known to be involved in the recognition of muramyl dipeptide (MDP), a compound of the bacterial peptidoglycan wall. NOD2 is suspected to be associated with inflammatory diseases such as Crohn's disease and Blau's syndrome. Recently, NOD2 receptor was shown to have the capacity to recognize viral single-stranded RNA motifs, such as Influenza A virus. However, although the antimicrobial functions of NOD2 are now supported by numerous studies, its role in the inflammatory response remains to be clarified. In patients with Crohn disease, it is unclear whether the mutations in NOD2 lead to an inability to control bacterial clearance, or if the inflammation results from a non-regulation of the inflammatory response. In our laboratory, we highlighted that MDP treatment could control immune homeostasis in various inflammatory models in mice. The purpose of this work was to investigate the cell populations and the eventual mechanisms underlying the activation of the NOD2 pathway by MDP and determine their implications for controlling the inflammatory response using different murine models. These studies allowed us to deepen the various potential mechanisms as well as the cell populations involved in the immune response linked to the activation of NOD2 by MDP. The results underline the promising role of the NOD2 pathway in the control of inflammation. Indeed, we highlighted the role of NOD2 in the development of Ly6Clow patrolling monocytes, alveolar macrophages and Treg cells and their involvement in the regulation of inflammation, during influenza A virus infection. This work has therefore increased our understanding of the NOD2 pathway and its beneficial effects in the control of inflammation and suggests that it could be an interesting therapeutic target to treat inflammatory and viral diseases
Document Type: Thèse de doctorat
Issue Date: 2018
Open Access Date: 10 October 2018
Permalink: http://hdl.handle.net/20.500.11794/31603
Grantor: Université Laval
Collection:Thèses et mémoires

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