VirulentSalmonella entericaSerovar Typhimurium Evades Adaptive Immunity by Preventing Dendritic Cells from Activating T Cells

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Abstract
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 entericaserovar 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 virulentSalmonellaapplies in vivo to prevent activation of adaptive immunity. In addition, this attribute of virulentSalmonellarequires functional expression of a type three secretion system (TTSS) and effector proteins encoded within theSalmonellapathogenicity island 2 (SPI-2). In contrast to wild-type virulentSalmonella, 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 virulentSalmonella. Our data suggest that impairment of DC function by the activity of SPI-2 gene products is crucial forSalmonellapathogenesis.

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