Abstract
BackgroundThe eradication of facultative intracellular bacterial pathogens, like Salmonella typhi, requires the concerted action of both the humoral immune response and the cytotoxic CD8+ T cell response. Dendritic cells (DCs) are considered to orchestrate the cytotoxic CD8+ T cell response via cross-presentation of bacterial antigens onto MHC class I molecules. Cross-presentation of Salmonella by DCs however, is accompanied by the induction of apoptosis in the DCs. Besides antibody production, B cells are required to clear Salmonella infection for other unknown reasons.Methodology/Principal FindingsHere we show that Salmonella-specific B cells that phagocytose Salmonella upon BCR-ligation reactivate human memory CD8+ T cells via cross-presentation yielding a Salmonella-specific cytotoxic T cell response. The reactivation of CD8+ T cells is dependent on CD4+ T cell help. Unlike the DCs, B cell-mediated cross-presentation of Salmonella does not coincide with apoptosis.Conclusions/SignificanceB cells form a new player in the activation of the cytotoxic effector arm of the immune response and the generation of effective adaptive immunity in Salmonella infection.
Highlights
Salmonella is a pathogenic bacterium that causes severe disease in mice and man
We investigated whether Salmonella-infected B cells are capable to induce a cytotoxic CD8+ T cell response
To study which kind of help CD4+ T cells provide for CD8+ T cell proliferation, we looked at the requirement of IL-2, by adding blocking antibodies to the culture of infected B cells and CD4+ and CD8+ T cells
Summary
Salmonella is a pathogenic bacterium that causes severe disease in mice and man. Salmonella typhi (Salmonella enterica serovar Typhi) causes invasive diseases in human, which has many features in common with Salmonella typhimurium in mice. One way to infect the host cells is via sampling of bacteria by DCs in the intestine. Like other Gram-negative bacteria, Salmonella uses specific virulence factors to invade other cell types, called the Type III Secretion System (TTSS). SPI-1 is associated with invasion of intestinal epithelia and enhanced intestinal inflammation in the infected host [7,8]. SPI-2 modulates intracellular trafficking and enables replication within a modified vacuolar compartment, called the Salmonella-containing vacuole (SCV) [9,10,11] and enhances inflammation during enteric phase [12,13]. The eradication of facultative intracellular bacterial pathogens, like Salmonella typhi, requires the concerted action of both the humoral immune response and the cytotoxic CD8+ T cell response. B cells are required to clear Salmonella infection for other unknown reasons
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