Browsing by Author "Tobar, Jaime A."
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- ItemSalmonella escape from antigen presentation can be overcome by targeting bacteria to Fc gamma receptors on dendritic cells.(2004) Tobar, Jaime A.; González, Pablo A.; Kalergis, Alexis M.Dendritic cells (DCs) are professional APCs with the unique ability to activate naive T cells, which is required for initiation of the adaptive immune response against pathogens. Therefore, interfering with DC function would be advantageous for pathogen survival and dissemination. In this study we provide evidence suggesting that Salmonella enterica serovar typhimurium, the causative agent of typhoid disease in the mouse, interferes with DC function. Our results indicate that by avoiding lysosomal degradation, S. typhimurium impairs the ability of DCs to present bacterial Ags on MHC class I and II molecules to T cells. This process could correspond to a novel mechanism developed by this pathogen to evade adaptive immunity. In contrast, when S. typhimurium is targeted to FcgammaRs on DCs by coating bacteria with Salmonella-specific IgG, bacterial Ags are efficiently processed and presented on MHC class I and class II molecules. This enhanced Ag presentation leads to a robust activation of bacteria-specific T cells. Laser confocal microscopy experiments show that virulent S. typhimurium is rerouted to the lysosomal degradation pathway of DCs when internalized through FcgammaR. These observations are supported by electron microscopy studies demonstrating that internalized S. typhimurium shows degradation signs only when coated with IgG and captured by FcgammaRs on DCs. Therefore, our data support a potential role for bacteria-specific IgG on the augmentation of Ag processing and presentation by DCs to T cells during the immune response against intracellular bacteria.
- ItemThe capacity of Salmonella to survive inside dendritic cells and prevent antigen presentation to T cells is host specific(WILEY-BLACKWELL, 2008) Bueno, Susan M.; Gonzalez, Pablo A.; Carreno, Leandro J.; Tobar, Jaime A.; Mora, Guido C.; Pereda, Cristian J.; Salazar Onfray, Flavio; Kalergis, Alexis M.Infection with Salmonella enterica serovar Typhimurium (S. Typhimurium) causes a severe and lethal systemic disease in mice, characterized by poor activation of the adaptive immune response against Salmonella-derived antigens. Recently, we and others have reported that this feature relies on the ability of S. Typhimurium to survive within murine dendritic cells (DCs) and avoid the presentation of bacteria-derived antigens to T cells. In contrast, here we show that infection of murine DCs with either S. Typhi or S. Enteritidis, two serovars adapted to different hosts, leads to an efficient T-cell activation both in vitro and in vivo. Accordingly, S. Typhi and S. Enteritidis failed to replicate within murine DCs and were quickly degraded, allowing T-cell activation. In contrast, human DCs were found to be permissive for survival and proliferation of S. Typhi, but not for S. Typhimurium or S. Enteritidis. Our data suggest that Salmonella host restriction is characterized by the ability of these bacteria to survive within DCs and avoid activation of the adaptive immune response in their specific hosts.