House dust mites (HDMs) induce allergic asthma in sensitized individuals, although how HDMs activate immature mucosal dendritic cells (DCs) to render the T helper cell type 2 (Th2)-mediated immune response is unclear. In this study, our results showed a significant calcium-dependent lectin binding of Dermatophagoides pteronyssinus (Der p) extracts to DC-specific intercellular adhesion molecule-3-grabbing nonintegrin (DC-SIGN), the C-type lectin receptors (CLRs) of DCs. Moreover, monocyte-derived DCs (MDDCs) of Der p-sensitized asthmatics (AS) exhibited decreased expression of DC-SIGN, increased endocytosis, and impaired differentiation of DC precursors. The Der p-induced downregulation of DC-SIGN expression in the differentiation of immature MDDCs may be because of the internalization of Der p-DC-SIGN complex. MDDCs of AS produced more interleukin (IL)-6 and less IL-12p70 cytokines when stimulated with lipopolysaccharide (LPS) or Der p than those of nonallergic controls (NC). In the co-culture experiments, MDDCs pretreated with Der p induced GATA-3 expression and IL-4 cytokine productions in naive CD4 T cells. These effects of Der p on the differentiation and function of MDDCs could be partially blocked by anti-DC-SIGN antibodies. In conclusion, our results suggest a critical step of allergen sensitization that involves CLRs in the innate immune response of DCs, which may provide a therapeutic or preventive potential for allergic asthma.
All Science Journal Classification (ASJC) codes
- Immunology and Allergy