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Impact de l'infection par Porphyromonas gingivalis sur la réponse inflammatoire locale et systémique

Abstract : The mechanisms involved in the initiation and development of periodontitis, as well as the dissemination of periodontal pathogens via the systemic circulation and their effects at the vascular level, remain poorly described. Chronic infection has been identified as a potential mechanism involved in atherothrombosis worsening. Indeed, Porphyromonas gingivalis (P.gingivalis) is considered to be a major periodontal pathogen involved in the onset and development of the diseases. Its ability to disrupt the epithelial barrier, as well as the endothelium barrier, and to induce a sustained inflammatory response contributes to tissue destruction. In this thesis, we evaluated the effects of P.gingivalis on apoptosis and inflammation of epithelial cells (GEC), fibroblasts (FB) and in a 3D model of microtissues (MT), as well as in endothelial cells (EC). Finally, we evaluated its role in the signaling-related inflammatory response via TLR-2 and TLR-4 and its five TIR-domain-containing adaptors proteins (TIR). We have shown that P.gingivalis is able to activate the inflammation and host-immune response, resulting in the destruction of the periodontium through modulation of primordial biological processes of various cell types, such as apoptosis (modulation of apoptosome Apaf-1 and its inhibitor XIAP), cell cycle (P53, P21, CDK4), inflammation (modulation of TLR-2, TLR-4, its MAL and TRAM adaptors proteins and inflammatory proteins such as TNF-α) , allowing it to escape from the immune system contributing to periodontal destruction and its systemic dissemination. The discovery of new mechanisms or new molecular targets affected by this pathogen will allow us to develop new therapeutic strategies.
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Submitted on : Tuesday, August 25, 2020 - 10:13:35 AM
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Isaac Maximiliano Bugueno Valdbenito. Impact de l'infection par Porphyromonas gingivalis sur la réponse inflammatoire locale et systémique. Microbiologie et Parasitologie. Université de Strasbourg, 2019. Français. ⟨NNT : 2019STRAJ090⟩. ⟨tel-02921380⟩

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