alpha-defensins1-3 are potent antimicrobial molecules that also link innate and adaptive immunity, depending on the concentration range. However, their effects on the biology of human DCs remain largely unknown. We analyzed the impact of different concentrations of alpha-defensins1-3 on the maturation and differentiation of monocyte-derived DCs (MDDCs). Low doses of alpha-defensins1-3 up-regulated CD83, CD86 and HLA-DR expression, increased TNF-alpha, IL-1beta, IL-12p40, IL-10 and IL-8 secretion, and slightly augmented allostimulatory capacity. By contrast, high doses down-regulated CD86 and HLA-DR expression, TNF-alpha, IL-1beta, IL-12p40 and IL-10 secretion and allostimulatory capacity, whereas strongly up-regulated IL-8. Furthermore, during the MDDC differentiation process, high doses of alpha-defensins1-3 affected CD14, CD11c and CD86 expression and strongly up-regulated IL-8. Results suggest that alpha-defensins1-3 might modulate the maturation and differentiation of MDDCs in vivo and therefore could be of special interest in the field of vaccine development.