Salmonella enterica Serovar Typhi Plasmid Impairs Dendritic Cell Responses to Infection
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Salmonella enterica serovar Typhi (S. typhi) evades from innate immunity by expression of a variety of pathogenic factors. The “pRST98” plasmid of S. typhi is involved in multidrug-resistant and virulence of S. typhi. However, its exact effect on host cell function remains elusive. Dendritic cells (DCs) play an important role in shaping immune response against Salmonella. For the purpose of investigation whether pRST98 might target DCs involved in adaptive immune response, murine DCs were infected with S. typhi wild type and mutant strains. S. typhi stimulation resulted in up-regulation of costimulatory molecules on DCs. S. typhi wild type resulted in decreased up-regulation of CD40, CD80, and CD86 expression. Experiments with S. typhi pRST98 mutant (S. typhi-Δ-pRST98) and S. typhi-Δ-pRST98 with a complemented plasmid encoding pRST98 (S. typhi-c-pRST98) revealed that pRST98 accounts for inhibition of surface molecule expression and functional maturity. S. typhi-Δ-pRST98 gave maximal levels of IL-12 and IFN-γ release compared with wild type S. typhi or the complemented strains. In contrast to IL-12 and IFN-γ, IL-10 secretion by S. typhi-Δ-pRST98-infected DCs was significantly lower than induction by S. typhi wild type. This indicates that immunity in response to pRST98 is skewed away from a protective Th1 response. Moreover, infection with S. typhi-Δ-pRST98 induced autophagy in DCs. We herein demonstrate S. typhi pRST98 plays essential roles in modulating DCs maturation, activation, inflammatory responses, and autophagy. Together, these data prove that pRST98 targets functions of DCs that are required for T-cell activation. This might contribute to evasion of adaptive immune responses by S. typhi.
KeywordsTyphoid Fever Costimulatory Molecule Functional Maturity Complementary Strain Cytokine Expression Profile
This study was supported by Natural Science Foundation of China (No. 30972768), Special Research Fund for the Doctoral Program of High Education (No. 20103201110009), Natural Science Foundation of Jiangsu province (No. BK2011286), Qinglan Project of Jiangsu Province (No. SR13400211) and Program sponsored for scientific innovation research of college graduate in Jiangsu province (No. CX10B_042Z).