Human blood dendritic cells from allergic subjects have impaired capacity to produce interferon-α via toll-like receptor 9

Background: High-affinity IgE receptor (FcεRI) expression on blood dendritic cells reportedly correlates with serum IgE levels. Our studies demonstrate that plasmacytoid dendritic cells (pDCs) secrete pro-inflammatory cytokines (IL-6, TNF-α) following FcεRI stimulation - a mode of activation that simultaneously reduces expression of Toll-like receptor 9 (TLR9). Whether or not TLR9 and/or FcεRI levels and their function on dendritic cells relate to allergic status is unknown. Objective: The aim of this study is to compare the innate (TLR9-mediated) immune response of human pDCs to TLR9 and FcεRIα receptor expression in allergic and non-allergic subjects. Methods: Basophil-depleted mononuclear cell fractions containing pDCs were prepared from peripheral blood of allergic and non-allergic subjects. Intracellular TLR9 and surface FcεRIα expression in blood dendritic cell antigen-2-positive cells were determined by flow cytometry. Activating anti-IgE antibody, anti-FcεRIα antibody, and TLR9 agonist were used to stimulate cell suspensions, with cytokine levels determined by ELISA. Results: No difference in the frequency of pDCs was detected among allergic (n=9) vs. non-allergic (n=11) subjects (P=0.261). While there was also no difference in the baseline expression of TLR9, pDCs from allergic subjects produced sixfold less IFN-α when stimulated with CpG (P=0.002). Conversely, there was higher FcεRIα expression (P=0.01) on the pDCs of allergic subjects. Conclusions: Impaired TLR9-dependent immune responses in human pDCs are associated with allergic status and inversely correlated with FcεRIα expression. This impaired innate immune response among dendritic cells of allergic subjects may lead to more targeted therapeutic approaches and could provide a better understanding of the mechanisms underlying conventional and CpG-based immunotherapy.