An investigation into the consequences of Salmonella infection of murine macrophages and dendritic cells : relevance to reactive arthritis
Reactive arthritis (ReA) is a sterile joint inflammation triggered by bacterial infection and is associated with the MHC class I molecule HLA-B27. Bacterial antigens have been detected in synovial tissues from ReA patients, but how they are transported to the joints from the site of infection is not known. In this project, we have tested the role of infected macrophages and dendritic cells as carriers of bacterial antigens in a mouse model for ReA. Bone marrow derived macrophages (BMMac) and dendritic cells (BMDC) were infected with Salmonella, a known causative agent of ReA, and adoptively transferred to HLA-B27 transgenic mice. We found a differential migration profile for Salmonella infected macrophages vs dendritic cells. In contrast to their uninfected counterparts, both populations emigrated significantly from the peritoneal cavity after intraperitoneal (i.p.) injection. Salmonella-infected BMDC showed a significantly increased ability to migrate to secondary lymphoid organs (SLO) (spleen and mesenteric lymph nodes). Moreover, results from CCR7 deficient mouse clearly showed that the migration of infected BMDC to the mesenteric lymph nodes (MLN), but not the spleen, was mediated by CCR7. Unlike BMDC, Salmonella infected BMMac were prone to migrate to inflamed joints. Although both BMDC and BMMac were able to present bacterial-derived peptides and stimulate antigen experienced cytotoxic T cells in vitro, only BMDC were capable of activating antigen specific naive T cells. By co-transfer HLA-B27 transgenic BMDC and naive T cells from GRb transgenic mice, which express a HLA-B27-restricted TCR specific for an influenza peptide, BMDC infected with recombinant Salmonella expressing the flu epitope were shown to induce T cells activation in vivo. The results of this study suggest distinct roles for macrophages and dendritic cells as antigen transporters following Salmonella infection, and have implications for both the pathogenesis of ReA, and the generation of anti-Salmonella immunity.