RésuméBrucella spp. are facultative intracellular bacteria responsible for brucellosis, a chronic zoonotic disease which cause abortion in infected cattle. Brucellosis is transmitted to humans through the consumption of infected animal products or aerosols. There are currently no safe or efficient vaccine, and the treatment involves long term antibiotics uptake. Following intranasal infection, Bru.cella melitensis infects primarily alveolar macrophages and persists in the lungs for a few days before being progressively cleared out and disseminating through the organism. Previous studies showed that the control of Brucella in the lungs involves T H17 mediated responses at 5 days post infection, and T Hl mediated responses in later times. In the chronic phase of infection, Brucella settles in the spleen, sheltered from the immune response. That is why the control of Bru.cella infection is crucial during its early stages. Our objectives were to characterize the early times of infection (0-48 hours) in vivo following intranasal inoculation of Brucella melitensis in mice models. We used three strategies to address this problem : confirming by flow cytometry the phenotype of the lungs infected cells in early times of infection, visualizing Bru.cella growth and division in vivo by microscopy,
and identif ying a role of the immune response in the control of the infection by comparing the resistance of various mice deficient for key elements of the immune system. During this study, we used eFluor 670 to label the membrane of the bacteria. This allowed us to formally identify by flow cytometry the Brucella-infected cells as alveolar macrophages. This staining also hel ped us to discriminate mother cell from daughter cells in vivo by microscopy. Finally, we demonstrated that T cells were implicated in the early control of
intranasal Brucella infection, and that allergie asthma favors Brucella growth in the lungs.
|la date de réponse||2017|
|Superviseur||Eric MURAILLE (Promoteur), JEAN-JACQUES LETESSON (Copromoteur) & Xavier De Bolle (Copromoteur)|