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Infection and Immunity, November 2006, p. 6438-6448, Vol. 74, No. 11
0019-9567/06/$08.00+0 doi:10.1128/IAI.00063-06
Copyright © 2006, American Society for Microbiology. All Rights Reserved.
Virulent Salmonella enterica Serovar Typhimurium Evades Adaptive Immunity by Preventing Dendritic Cells from Activating T Cells
Jaime A. Tobar,1
Leandro J. Carreño,1
Susan M. Bueno,1
Pablo A. González,1
Jorge E. Mora,1
Sergio A. Quezada,1 and
Alexis M. Kalergis1,2,3*
Departamento de Genética Molecular y Microbiología, Facultad de Ciencias Biológicas,1
Departamento de Reumatología, Facultad de
Medicina, Pontificia Universidad Católica de Chile, Santiago, Chile,2
Department of Microbiology and Immunology, Albert Einstein College of Medicine, New York, New York3
Received 12 January 2006/
Returned for modification 28 February 2006/
Accepted 26 July 2006
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 naïve 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.
* Corresponding author. Mailing address: Facultad de Ciencias Biológicas,
Pontificia Universidad Católica de Chile, Alameda #340,
Santiago, Chile. Phone: 56-2-686-2842. Fax: 56-2-222-5515. E-mail:
akalergis{at}bio.puc.cl.
Editor:
J. L. Flynn
Infection and Immunity, November 2006, p. 6438-6448, Vol. 74, No. 11
0019-9567/06/$08.00+0 doi:10.1128/IAI.00063-06
Copyright © 2006, American Society for Microbiology. All Rights Reserved.
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