Overexpression of Dendritic Cell-Specific Intercellular Adhesion Molecule-3-Grabbing Nonintegrin in Dendritic Cells Protecting against Aspergillosis

Abstract

Background: Dendritic cells (DCs) play an important role in host defense against pathogen infection. DC-specific intercellular adhesion molecule-3-grabbing nonintegrin (SIGN) is a group II C-type lectin receptor and specifically expressed on the surface of DCs. This study aimed to determine whether DC-SIGN affects intracellular signaling activation, Th1/Th2 imbalance and aspergillus immune evasion in aspergillus infection, and explore the application of DC-SIGN-modified DCs in immunotherapy. Methods: DCs were first obtained from the mononuclear cells of peripheral blood. The interferon (IFN)-? and dexamethasone (Dex) were used to stimulate DCs. The expression of DC-SIGN, Th1 and Th2 cytokines, and the capacity of DCs in stimulating T cells proliferation and phagocytosis, and nuclear factor (NF)-?B activation were analyzed. In addition, adenovirus expression vector Ad-DC-SIGN was generated to transfect DCs. Mannan was used to block DC-SIGN signaling for confirming the involvement of DC-SIGN function in Aspergillus fumigatus (Af)-induced DCs maturation. The unpaired, two-tailed Student?s t-test was used in the comparisons between two groups. Results: Exogenous IFN-? could activate Af-induced DCs and promote the Th0 cells toward Th1 profile (interleukin [IL]-12 in IFN-?/Af group: 50.96 ± 4.38 pg/ml; control/Af group: 29.70 ± 2.00 pg/ml, t = 10.815, P < 0.001). On the other hand, Dex inhibited the secretion of Th2 cytokines (IL-10 in Dex/Af group: 5.27 ± 0.85 pg/ml; control/Af group: 15.14 ± 1.40 pg/ml, t = 14.761, P < 0.001)), and successfully caused immunosuppression. After transfection with Ad-DC-SIGN, DCs have improved phagocytosis (phagocytosis rates in Ad-DC-SIGN group: 74.0% ± 3.4%; control group: 64.7% ± 6.8%, t = 3.104, P = 0.013). There was more Th1 cytokine secreted in the Af-induced DC-SIGN modified DCs (IL-12 in Ad-DC-SIGN/Af group: 471.98 ± 166.31 pg/ml; control/Af group: 33.35 ± 5.98 pg/ml, t = 6.456, P = 0.001), correlated to the enhanced NF-?B activation. Conclusion: Overexpressing DC-SIGN in DCs had a protective function on aspergillosis.