Background： Dendritic cells （DCs） play an important role in host defense against pathogen infection. DC-specific intercellular adhesion moleeule-3-grabbing nonintegrin （SIGN） is a group II C-type lectin receptor ...Background： Dendritic cells （DCs） play an important role in host defense against pathogen infection. DC-specific intercellular adhesion moleeule-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 mononuelear ceils of peripheral blood. The interferon （IFN）-γand 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-y could activate Af-induced DCs and promote the Th0 cells toward Th 1 profile （interleukin [IL]- 12 in I FN-y/Af group： 50.96 ± 4.38 pg/ml; control/Afgroup： 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. Alier 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-KB activation. Conclusion： Overexpressing DC-SIGN in DCs had a protective function on aspergillosis.展开更多
基金The study was supported by a grant from the National Natural Science Foundation of China （No. 30772019）.
文摘Background： Dendritic cells （DCs） play an important role in host defense against pathogen infection. DC-specific intercellular adhesion moleeule-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 mononuelear ceils of peripheral blood. The interferon （IFN）-γand 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-y could activate Af-induced DCs and promote the Th0 cells toward Th 1 profile （interleukin [IL]- 12 in I FN-y/Af group： 50.96 ± 4.38 pg/ml; control/Afgroup： 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. Alier 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-KB activation. Conclusion： Overexpressing DC-SIGN in DCs had a protective function on aspergillosis.
