Dendritic cell interactions with Gram negative bacteria

Detta är en avhandling från Mattias Svensson, Sölvegatan 19, 223 62 Lund

Sammanfattning: The interaction between murine bone marrow-derived dendritic cells (DC) and the Gram negative bacteria Salmonella typhimurium and Escherichia coli have been characterised. These studies showed that DC phagocytosed and processed S. typhimurium and E. coli expressing defined epitopes for peptide presentation on major histocompatibility complex class I (MHC-I) and class II (MHC-II) molecules. Processing of bacterial antigens for MHC-I presentation occurred by the classical MHC-I pathway as demonstrated by the requirement for the transporter associated with antigen processing (TAP), the proteasome and newly synthesised MHC-I molecules. Pulsing DC with S. typhimurium or E. coli also resulted in DC maturation as assessed by the reduced capacity to present antigens from a subsequent encounter with bacteria, and by upregulating surface expression of MHC and costimulatory molecules. Finally, transfer of Salmonella-pulsed DC into naive mice activated interferon-g-producing CD4+ and CD8+ T cells and cytotoxic CD8+ T cells specific for Salmonella antigens. Together these data demonstrate that DC can phagocytose and process S. typhimurium and E. coli into peptides for MHC presentation an may have a role in induction of Salmonella specific T cells in vivo.

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