Human defensins increase the frequency of activated CD91high monocyte-derived dendritic cells

PURPOSE: We investigated the expression of the polyfunctional receptor CD91 on monocyte-derived dendritic cells (moDCs) and the role of defensins in the activation of moDCs based on their level of CD91 expression. METHODS: Monocytes were obtained from human Peripheral Blood Mononuclear Cells (PBMCs) and cultured in the presence of rhGMCSF and rhIL-4. These immature moDCs were stimulated for 18 hr by full-length rHNP-1, rHBD-1 and LPS and characterized by flow cytometry. RESULTS: Two different subsets of moDCs were observed based on their CD91 expression: CD91low moDCs and CD91high moDCs. Although a small subset of moDCs, CD91high moDCs showed higher levels of the activation and maturation markers compared to CD91low moDCs. Interestingly, the frequency of CD91high moDCs increased by ~50-fold after rHNP-1 and rHBD stimulation, while LPS stimulation decreased it by ~35-fold. Our group previously demonstrated that recombinant human defensins activated moDCs (1). Furthermore, we investigated whether CD91low and CD91high moDC subsets undergo activation/maturation upon different stimulation. We found that rHNP-1 induced significantly higher levels of CD80, CD40 and HLA-DR on CD91high moDCs compared to CD91low moDCs, while rHBD-1 increased significantly the expression of CD83 and HLA-DR molecules on CD91high moDCs compared to CD91low moDCs. In contrast, LPS stimulation did not change the expression of these markers on CD91high and CD91low moDC subsets. DISCUSSION: We described two different subsets of moDCs based on their different CD91 expression and their activation/maturation status, suggesting that moDCs represent a heterogeneous cell population. Of note, defensins stimulation increases CD91high moDCs frequency and maintains the CD91high moDCs higher activation/maturation status compared to CD91low moDCs suggesting that CD91high moDCs are more prompt to respond to CD91-ligands. CONCLUSIONS: The presence of two distinct subsets of moDCs suggests a potential plasticity of dendritic cells in the immune response. In particular, CD91high moDCs may represent a useful adjunct to therapeutic strategy to potentiate antimicrobial and antitumor immune response. BIBLIOGRAPHY 1. Presicce, P., Giannelli, S., Taddeo, A., Villa, M. L., Della Bella, S. (2009) Human defensins activate monocyte-derived dendritic cells, promote the production of proinflammatory cytokines, and up-regulate the surface expression of CD91. Journal of leukocyte biology 86, 941-8.