Functional modulation of human monocytes derived DCs by anaphylatoxins C3a and C5a

Anaphylatoxins C3a and C5a are important modulators for dendritic cell activation and function in mice. In order to verify the significance of these observations in man, we have investigated the functional modulation of human monocytes derived DCs by C3a and C5a. Here we report that engagement of C3aR or C5aR on human monocytes derived DCs (moDCs) enhances the cell activation and their capacity for allostimulation. In addition, we show that intracellular production of cAMP is reduced and PI3K/AKT, ERK and NF-κB signalling is increased following stimulation with C3a or C5a, identifying intracellular signalling pathways that could convert cell surface C3aR and C5aR engagement into changes in moDC functions. Our data provide evidence that human DCs are equipped to react to C3a/C5a and undergo phenotypic change as well as functional modulation. Complement offers a potential route to modulate human DC function and regulate T cell mediated immunity.