Immune complex-induced enhancement of bacterial antigen presentation requires Fcgamma receptor III expression on dendritic cells.
Dendritic cells (DCs) are capable of initiating adaptive immune responses against infectious agents by presenting pathogen-derived antigens on MHC molecules to naïve T cells. Because of their key role in priming adaptive immunity, it is expected that interfering with DC function would be advantageous to the pathogen. We have previously shown that Salmonella enterica serovar Typhimurium (ST), is able to survive inside DCs and interfere with their function by avoiding activation of bacteria-specific T cells. In contrast, when ST is targeted to Fcgamma receptors on the DC surface, bacteria are degraded and their antigens presented to T cells. However, the specific Fcgamma receptor responsible of restoring presentation of antigens remains unknown. Here, we show that IgG-coated ST was targeted to lysosomes and degraded and its antigens presented on MHC molecules only when the low-affinity activating FcgammaRIII was expressed on DCs. FcgammaRIII-mediated enhancement of Ag presentation led to a robust activation of T cells specific for bacteria-expressed antigens. Laser confocal and electron microscopy analyses revealed that IgG-coated ST was rerouted to the lysosomal pathway through an FcgammaRIII-dependent mechanism. PI-3K activity was required for this process, because specific inhibitors promoted the survival of IgG-coated ST inside DCs and prevented DCs from activating bacteria-specific T cells. Our data suggest that the DC capacity to efficiently activate T cells upon capturing IgG-coated virulent bacteria is mediated by FcgammaRIII and requires PI-3K activity.
Herrada
Andrés A
AA
Departamento de Genética Molecular y Microbiología, Facultad de Ciencias Biológicas and Departamento de Reumatología, Facultad de Medicina, Pontificia Universidad Católica de Chile, Santiago E-8331010, Chile.
Contreras
Francisco J
FJ
Tobar
Jaime A
JA
Pacheco
Rodrigo
R
Kalergis
Alexis M
AM
D000936:Antigen-Antibody Complex; D000942:Antigens, Bacterial / Q000276:immunology*; D003713:Dendritic Cells / Q000201:enzymology / Q000276:immunology*; D008247:Lysosomes / Q000276:immunology; D019869:Phosphatidylinositol 3-Kinases / Q000378:metabolism; D017452:Receptors, IgG / Q000276:immunology* / Q000378:metabolism; D012486:Salmonella typhimurium / Q000276:immunology / Q000472:pathogenicity; D014774:Virulence
D000936:Antigen-Antibody Complex; D000942:Antigens, Bacterial; D017452:Receptors, IgG; D019869:Phosphatidylinositol 3-Kinases