Presentation of Salmonella antigens by dendritic cells

Detta är en avhandling från Ulf Yrlid, Fredsgatan 2, 222 20 Lund

Sammanfattning: This study investigates the interaction between dendritic cells (DC) and the Gram negative intracellular bacterium Salmonella typhimurium. Using in vitro and in vivo approaches, the capacity of DC to directly and indirectly present antigens from Salmonella-infected cells, cytokine production by infected DC, and activation of bacteria-specific T cells was analyzed. These studies revealed differential modulation of splenic DC subsets with regard to in situ distribution, absolute number, and cytokine production in mice orally infected with S. typhimurium. DC loaded with Salmonella in vitro were also capable of eliciting Salmonella-specific CD4+ and CD8+ T cells after transfer into naïve mice, and DC were activated in mice infected with Salmonella. In addition, splenic DC infected with S. typhimurium in vitro produced IL-12 and TNF-a, and the number of splenic DC producing TNF-a increased in Salmonella-infected mice. Furthermore, all three splenic DC subsets were capable of engulfing and processing Salmonella for MHC-I and MHC-II presentation of bacterial peptides to T cells, both in vitro and in vivo. In addition to this capacity to directly present Salmonella antigens, DC could also act as bystander cells capable of presenting antigens from neighboring macrophages induced to undergo apoptotic death following infection with Salmonella expressing the Type III secretion system. Together these data suggest that DC are key antigen presenting cells important in activating Salmonella-specific immunity.

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