Physiopathologie de l infection à Legionella pneumophila dans un modèle expérimental murin

Abstract

To progress in the understanding of L. pneumophila infection, we investigated host-pathogen interaction in vitro through lung epithelial cell cultures and in vivo through an A/J murine model focusing on two aspects: the studies of alveolar-capillary barrier injury and lung inflammatory response. Three parts have been developed: 1) a study of the mechanisms leading to L. pneumophila attachment to respiratory epithelia; 2) a study of virulence factor type IV secretion system (Dot/Icm system) involvement in L. pneumophila pathogenesis; 3) a primary characterization of mucosal innate response. The main results of this work are : -in vitro, the zinc ion is an important co-factor of L. pneumophila adherence to alveolar type II pneumocytes via a protein adhesin. -In vivo, sulphated saccharide heparin co-instilled intratracheally with L. pneumophila challenge has a protective effect on the alveolar-capillary barrier and prevents bacterial dissemination. It tends to confirm the competitive inhibition by heparin of L. pneumophila attachment to lung epithelium in vivo, and point to the possible involvement of a heparan-sulfate adhesin in L. pneumophila binding to pneumocytes. -In vivo, L. pneumophila Dot/Icm system of serogroup 1 strains Lens and Paris is central to pathogenesis and is associated with the development of acute lung injury, lung bacterial replication and systemic spread. -In vivo, at 4 and 48 hours post-infection by L. pneumophila both gene expressions of lung -defensins mBD-1 and mBD-3 were detected in a constitutive and inducible way respectively. However, the absence of ccl20 gene expression was observed, a key chemokine for dendritic cells recruitment after bacterial infectionLYON1-BU.Sciences (692662101) / SudocSudocFranceF