Résumé
Brucellae spp. (a-proteobacteria) are Gram-negative intracellular bacteria that cause brucellosis, a worldwide zoonosis. In animals, the disease is characterized by abortion in females and infertility in males. Human is an accidental host who can be chronically infected. In this master thesis, we study the Brucella melitensis 16M strain, that infects goat and sheep. We investigate the immune response of rnice fo llowing intra-dermal (ID) infection. This experimental model rnimics the natural Bruce fla infection by direct contact between skin lesion and infected tissue or fluid, which has been reported in farmers, vets or butchers. The main objectives of this master thesis are (i) the characterization of the course of the intradermal (ID) B. melitensis infection in wild type C57BL/6 rnice, (ii) the phenotypic characterization of infected cells in the skin and draining lymph node, (iii) the identification of the T helper subclasses of immune response controlling the intra-dermal infection and (iv) the identification of lymphoid cells involved in the control of primary and secondary ID infections. Our results showed that following ID infection, B. melitensis actively multiplies in skin lesion and disserninate in draining lymph node ( dLN) and spleen to reach a peak: of bacterial load at 3 days post-infection. At 50 days, B. melitensis is almost completely eliminated from skin lesion and dLN but persists in spleen, suggesting that the immune system is able to efficiently control its growth in skin tissues. In the lesion, only a few fraction of infected cells appears to be positive for MHCII, CDllc and Ly-6G markers, suggesting that infected cells at early times postinfection are neither activated monocytes, nor dendritic cells, nor neutrophils, respectively. Using a battery ofmice genetically deficient for key elements of immune system, we observed that the IFN-y-mediated T helper (TH)l response is indispensable to control skin infection. During a primary infection, CD4+ T lymphocytes seem be the main cells controlling the infection. However, we demonstrate that the absence of a ~TCR+ lymphocytes can becompensated by yoTCR+ lymphocytes after a secondary infection. In addition, an important role ofB cells has been observed to control the bacteria during secondary, but not primary, infection.
| la date de réponse | 2016 |
|---|---|
| langue originale | Anglais |
| L'institution diplômante |
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| Superviseur | Eric MURAILLE (Promoteur) & JEAN-JACQUES LETESSON (Copromoteur) |