PMID- 17679697
OWN - NLM
STAT- MEDLINE
DCOM- 20071024
LR  - 20181113
IS  - 0027-8424 (Print)
IS  - 1091-6490 (Electronic)
IS  - 0027-8424 (Linking)
VI  - 104
IP  - 33
DP  - 2007 Aug 14
TI  - Immune complex-induced enhancement of bacterial antigen presentation requires 
      Fcgamma receptor III expression on dendritic cells.
PG  - 13402-7
AB  - 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 
      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.
FAU - Herrada, Andres A
AU  - Herrada AA
AD  - Departamento de Genetica Molecular y Microbiologia, Facultad de Ciencias 
      Biologicas and Departamento de Reumatologia, Facultad de Medicina, Pontificia 
      Universidad Catolica de Chile, Santiago E-8331010, Chile.
FAU - Contreras, Francisco J
AU  - Contreras FJ
FAU - Tobar, Jaime A
AU  - Tobar JA
FAU - Pacheco, Rodrigo
AU  - Pacheco R
FAU - Kalergis, Alexis M
AU  - Kalergis AM
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20070806
PL  - United States
TA  - Proc Natl Acad Sci U S A
JT  - Proceedings of the National Academy of Sciences of the United States of America
JID - 7505876
RN  - 0 (Antigen-Antibody Complex)
RN  - 0 (Antigens, Bacterial)
RN  - 0 (Receptors, IgG)
RN  - EC 2.7.1.- (Phosphatidylinositol 3-Kinases)
SB  - IM
MH  - *Antigen-Antibody Complex
MH  - Antigens, Bacterial/*immunology
MH  - Dendritic Cells/enzymology/*immunology
MH  - Lysosomes/immunology
MH  - Phosphatidylinositol 3-Kinases/metabolism
MH  - Receptors, IgG/*immunology/metabolism
MH  - Salmonella typhimurium/immunology/pathogenicity
MH  - Virulence
PMC - PMC1948949
COIS- The authors declare no conflict of interest.
EDAT- 2007/08/08 09:00
MHDA- 2007/10/25 09:00
PMCR- 2008/02/14
CRDT- 2007/08/08 09:00
PHST- 2007/08/08 09:00 [pubmed]
PHST- 2007/10/25 09:00 [medline]
PHST- 2007/08/08 09:00 [entrez]
PHST- 2008/02/14 00:00 [pmc-release]
AID - 0700999104 [pii]
AID - 7083 [pii]
AID - 10.1073/pnas.0700999104 [doi]
PST - ppublish
SO  - Proc Natl Acad Sci U S A. 2007 Aug 14;104(33):13402-7. doi: 
      10.1073/pnas.0700999104. Epub 2007 Aug 6.