Objective: Recent studies proposed a pathogenic role for C-reactive protein (CRP), an independent predictor of cardiovascular disease (CVD), in atherosclerosis. Therefore, we tested whether CRP may modulate dendritic cell (DC) function, since these professional antigen-presenting cells have been implicated in atherogenesis.Methods: Human monocyte-derived immature DCs were cultured with human CRP (0-60 mg/ml) for 24 h. Thereafter, activation markers were measured by flow-cytometry and after washing DCs were co-cultured with CFSE-labelled lymphocytes to measure T-cell proliferation and interferon-U secretion after 8 days.Results: Exposure to 60 mg/ml CRP (n = 5) induced an activated cell morphology and significant (CD40 increase MFI 5.23  0.28, P < 0.01 paired t-test; CD80 6.18  0.51, P < 0.01) to modest (CD83 1.38  0.17, P < 0.05, CCR7 1.60  0.29, P = 0.05) upregulation of DC activation markers. The expression of CD86 and HLA-DR was high, but not affected. T-lymphocytes incubated with CRP-pulsed DCs displayed increased interferon-U secretion and proliferation (P < 0.001). DC activation was concentration-dependent and detected from 2 mg/ml CRP; the maximum effect was equivalent to that seen with 0.1 mg/ml lipopolysaccharide (LPS). Polymyxin B abolished the LPS response, without influencing CRP effects. Finally, immunohistochemistry could demonstrate DC/CRP co-localisation in human atherosclerotic lesions. Conclusions: These findings suggest that CRP in plaques or found in the circulation of CVD patients could influence DC function during atherogenesis.