PMID- 17057096
OWN - NLM
STAT- MEDLINE
DCOM- 20061213
LR  - 20181113
IS  - 0019-9567 (Print)
IS  - 1098-5522 (Electronic)
IS  - 0019-9567 (Linking)
VI  - 74
IP  - 11
DP  - 2006 Nov
TI  - Virulent Salmonella enterica serovar typhimurium evades adaptive immunity by 
      preventing dendritic cells from activating T cells.
PG  - 6438-48
AB  - Dendritic cells (DCs) constitute the link between innate and adaptive immunity by 
      directly recognizing pathogen-associated molecular patterns (PAMPs) in bacteria 
      and by presenting bacterial antigens to T cells. Recognition of PAMPs renders DCs 
      as professional antigen-presenting cells able to prime naive T cells and initiate 
      adaptive immunity against bacteria. Therefore, interfering with DC function would 
      promote bacterial survival and dissemination. Understanding the molecular 
      mechanisms that have evolved in virulent bacteria to evade activation of adaptive 
      immunity requires the characterization of virulence factors that interfere with 
      DC function. Salmonella enterica serovar Typhimurium, the causative agent of 
      typhoid-like disease in the mouse, can prevent antigen presentation to T cells by 
      avoiding lysosomal degradation in DCs. Here, we show that this feature of 
      virulent Salmonella applies in vivo to prevent activation of adaptive immunity. 
      In addition, this attribute of virulent Salmonella requires functional expression 
      of a type three secretion system (TTSS) and effector proteins encoded within the 
      Salmonella pathogenicity island 2 (SPI-2). In contrast to wild-type virulent 
      Salmonella, mutant strains carrying specific deletions of SPI-2 genes encoding 
      TTSS components or effectors proteins are targeted to lysosomes and are no longer 
      able to prevent DCs from activating T cells in vitro or in vivo. SPI-2 mutant 
      strains are attenuated in vivo, showing reduced tissue colonization and enhanced 
      T-cell activation, which confers protection against a challenge with wild-type 
      virulent Salmonella. Our data suggest that impairment of DC function by the 
      activity of SPI-2 gene products is crucial for Salmonella pathogenesis.
FAU - Tobar, Jaime A
AU  - Tobar JA
AD  - Departamento de Genetica Molecular y Microbiologia, Facultad de Ciencias 
      Biologicas, Pontificia Universidad Catolica de Chile, Alameda #340, Santiago, 
      Chile.
FAU - Carreno, Leandro J
AU  - Carreno LJ
FAU - Bueno, Susan M
AU  - Bueno SM
FAU - Gonzalez, Pablo A
AU  - Gonzalez PA
FAU - Mora, Jorge E
AU  - Mora JE
FAU - Quezada, Sergio A
AU  - Quezada SA
FAU - Kalergis, Alexis M
AU  - Kalergis AM
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PL  - United States
TA  - Infect Immun
JT  - Infection and immunity
JID - 0246127
RN  - 0 (Bacterial Proteins)
RN  - 0 (Membrane Proteins)
RN  - 0 (SPI-2 protein, Salmonella)
RN  - 0 (SpiA protein, Salmonella typhimurium)
RN  - 0 (SpiC protein, Salmonella)
SB  - IM
MH  - Animals
MH  - Bacterial Proteins/genetics
MH  - Dendritic Cells/*immunology/*microbiology
MH  - Gene Deletion
MH  - *Immunity, Active/genetics
MH  - Lymphocyte Activation/genetics/*immunology
MH  - Membrane Proteins/genetics
MH  - Mice
MH  - Mice, Inbred C57BL
MH  - Mice, Transgenic
MH  - Salmonella typhimurium/genetics/immunology/*pathogenicity
MH  - T-Lymphocytes/*immunology/microbiology
MH  - Virulence/genetics/immunology
PMC - PMC1695529
EDAT- 2006/10/24 09:00
MHDA- 2006/12/14 09:00
PMCR- 2007/03/01
CRDT- 2006/10/24 09:00
PHST- 2006/10/24 09:00 [pubmed]
PHST- 2006/12/14 09:00 [medline]
PHST- 2006/10/24 09:00 [entrez]
PHST- 2007/03/01 00:00 [pmc-release]
AID - 74/11/6438 [pii]
AID - 0063-06 [pii]
AID - 10.1128/IAI.00063-06 [doi]
PST - ppublish
SO  - Infect Immun. 2006 Nov;74(11):6438-48. doi: 10.1128/IAI.00063-06.