Journal
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
Volume 104, Issue 33, Pages 13402-13407Publisher
NATL ACAD SCIENCES
DOI: 10.1073/pnas.0700999104
Keywords
Fc gamma receptors; phosphoinositide-3 kinase; Salmonella Typhimurium; T cells; antigen-presenting cells
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Dendritic cells (DCs) are capable of initiating adaptive immune responses against infectious agents by presenting pathogen-derived antigens on MHC molecules to naive 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 Fc gamma receptors on the DC surface, bacteria are degraded and their antigens presented to T cells. However, the specific Fc gamma 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 Fc gamma RIII was expressed on DCs. Fc gamma RIII-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 Fc gamma RIII-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 Fc gamma RIII and requires PI-3K activity.
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