Phagocytosis of bacteria by mouse bone marrow-derived dendritic cells affects their ability to process a heterologous soluble antigen in vitro

Sentinel dendritic cells are likely to encounter both live and dead bacteria at sites of infection. Although dendritic cells can phagocytose such bacteria, their principle role is not in bacterial killing but in stimulation of a subsequent adaptive immune response. In contrast, neutrophils at the site of infection play a major role in bacterial killing, in part via oxidative chlorination by myeloperoxidase products. In this study, the interaction between bacterial phagocytosis and the antigen processing function of dendritic cells is examined. Ingestion of heat-killed Salmonella typhimurium, or bacteria killed by oxidative chlorination, induces up-regulation of co-stimulatory molecules on dendritic cells, and strong stimulation of the TH1-inducing proinflammatory cytokines IL-12 and TNF-α. In contrast, induction of nitric oxide production is weak. Finally, phagocytosis of bacteria inhibits processing of protein antigen, but only if phagocytosis precedes exposure to antigen by 24 hours. Phagocytosis itself has no inhibitory effect on the concomitant processing and presentation of either protein or peptide antigen to T cells. These results demonstrate that both phagocytic and antigen processing pathways can operate simultaneously within dendritic cells, allowing these sentinel cells to operate effectively at the site of bacterial infection.