Antigen-Specific B Cells Reactivate an Effective Cytotoxic T Cell Response against Phagocytosed Salmonella through Cross-Presentation

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.

Selective Infection of Antigen-Specific B Lymphocytes by Salmonella Mediates Bacterial Survival and Systemic Spreading of Infection

“…Whether this explains the control of Salmonella replication in human primary B cells remains to be established. An effective CD8 + cytotoxic T cell response is essential to control Salmonella infection [32], [33], possibly to eliminate Salmonella hiding inside cells. Our data show that also systemic spreading of Salmonella will be limited by elimination of the intracellular bacteria in B cells.…”

Live Attenuated Human Salmonella Vaccine Candidates: Tracking the Pathogen in Natural Infection and Stimulation of Host Immunity

“…Upon infection of phagocytic and professional antigen presenting cells (i.e. macrophages and dendritic cells) Salmonella antigens are processed and presented for stimulation of CD4 and CD8 T cells, resulting in activation and differentiation of T helper (Th) 1, Th2 and Th17 cells(60–62), as well as T cytotoxic (Tc)(63, 64) and T regulatory (Treg) cells(65), which are believed to be essential for protection against disease (66). Natural infection also results in the induction of Th1 type CD4+ and CD8+ T cells that produce high levels of IFN-γ during acute and convalescent phases of infection(60).…”

Combined Induction Therapy with Rabbit Antithymocyte Globulin and Rituximab in Highly Sensitized Renal Recipients

“…There is also emerging evidence that B cells play a central role in the formation of tertiary lymphoid organs (TLOs) and the modulation of chronic rejection (Thaunat, 2011). RTX can impair B-cell regulation of T cells (such as CD8 + recall response) and CD4 + activation (Bouaziz et al, 2010;de Wit et al, 2010). Currently, it is also suggested that RTX may cause direct T-cell inactivation (Stroopinsky et al, 2012).…”