Overexpression of Dendritic Cell-Specific Intercellular Adhesion Molecule-3-Grabbing Nonintegrin in Dendritic Cells Protecting against Aspergillosis
摘要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)-γ and dexamethasone (Dex) were used to stimulate DCs.The expression ofDC-SIGN,Th 1 and Th2 cytokines,and the capacity of DCs in stimulating T cells proliferation and phagocytosis,and nuclear factor (NF)-κB 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-γ could activate Af-induced DCs and promote the Th0 cells toward Th 1 profile (interleukin [IL]-12 in IFN-γ/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/Afgroup: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 Thl 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-κB activation.Conclusion:Overexpressing DC-SIGN in DCs had a protective function on aspergillosis.
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