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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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