concanavalin-a and Bacteroidaceae-Infections

Porphyromonas gingivalis, a major periodontal pathogen, has been reported to be involved in atherogenesis. In order to further understand this pathogen's link with systemic inflammation and vascular disease, we investigated its influence on murine monocytes and macrophages from three different sources.. Concanavalin A-elicited peritoneal macrophages, peripheral blood monocyte-derived macrophages and WEHI 274.1 monocytes were infected with either P. gingivalis 381 or its non-invasive fimbriae-deficient mutant, DPG3.. Infection with P. gingivalis 381 markedly induced monocyte migration and significantly enhanced production of the pro-inflammatory cytokines, tumor necrosis factor-alpha and interleukin-6. Consistent with a role for this pathogen's major fimbriae and/or its invasive capacity, infection with DPG3 had a minimal effect on both monocyte attraction and pro-inflammatory cytokine production.. Since monocyte recruitment and activation are important steps in the development of vascular inflammation and atherosclerosis, these results suggest that P. gingivalis infection may be involved in these processes.

Topics: Animals; Bacteriological Techniques; Bacteroidaceae Infections; Cell Culture Techniques; Cell Line; Cell Movement; Chemotaxis, Leukocyte; Concanavalin A; Cytokines; Fimbriae, Bacterial; Hypercholesterolemia; Inflammation Mediators; Interleukin-6; Macrophage Activation; Macrophages; Macrophages, Peritoneal; Male; Mice; Mice, Inbred C57BL; Mice, Inbred Strains; Mitogens; Monocytes; Mutation; Porphyromonas gingivalis; Tumor Necrosis Factor-alpha

T cell antigen receptor zeta chain down-regulation and impaired in vitro T cell function have been described in cancer and autoimmune and infectious diseases. However, the immunological basis for this phenomenon is unknown. Sustained exposure to antigen and chronic systemic inflammation, factors shared by the various pathologies, might account for this phenomenon. We developed an in vivo experimental system that mimics these conditions and show that sustained exposure of mice to bacterial antigens was sufficient to induce T cell antigen receptor zeta chain down-regulation and impair T cell function, provided an interferon-gamma-dependent T helper type 1 immune response developed. This indicates zeta chain down-regulation could be a physiological response that attenuates an exacerbated immune response. However, it can act as a 'double-edged sword', impairing immune responses to chronic diseases.

Topics: Animals; Antigens, Bacterial; Bacteroidaceae Infections; Blotting, Western; Concanavalin A; Down-Regulation; Female; Flow Cytometry; Interferon-gamma; Ionophores; Lymphocyte Activation; Membrane Proteins; Mice; Mice, Inbred BALB C; Mice, Knockout; Microscopy, Confocal; Porphyromonas gingivalis; Receptors, Antigen, T-Cell; Specific Pathogen-Free Organisms; Tetradecanoylphorbol Acetate; Th1 Cells