Salmonella escape from antigen presentation can be overcome by targeting bacteria to Fc? receptors on dendritic cells

Tobar J.A.; González P.A.; Kalergis, A.M.

Keywords: model, electron, proteins, salmonella, mouse, survival, activation, animals, degradation, cells, antigen, lysosomes, flow, protein, cell, virulence, t-lymphocytes, mice, bacterial, microscopy, line, plasmids, experiment, receptor, laser, antigens, tissue, egg, typhimurium, confocal, article, phagocytosis, h-2, lysosome, cytometry, lymphocyte, immunoglobulin, igg, enterica, class, controlled, animal, presentation, study, 1, priority, nonhuman, journal, Receptors,, 2, major, G, Inbred, t, Antigens,, Mice,, C57BL, histocompatibility, typhi, Fc, dendritic, ovalbumin

Abstract

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 Fc?Rs 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 Fc?R. These observations are supported by electron microscopy studies demonstrating that internalized S. typhimurium shows degradation signs only when coated with IgG and captured by Fc?Rs 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 intracelluinr bacteria.

Más información

Título según SCOPUS: Salmonella escape from antigen presentation can be overcome by targeting bacteria to Fc? receptors on dendritic cells
Título de la Revista: JOURNAL OF IMMUNOLOGY
Volumen: 173
Número: 6
Editorial: AMER ASSOC IMMUNOLOGISTS
Fecha de publicación: 2004
Página de inicio: 4058
Página final: 4065
Idioma: English
URL: http://www.scopus.com/inward/record.url?eid=2-s2.0-4644333888&partnerID=q2rCbXpz
Notas: SCOPUS