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

Li-Yang LI; Hao-Ru ZHANG; Zhi-Long JIANG; Yan-Zhong CHANG; Chang-Zhou SHAO

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

Author: Li-Yang LI ¹ ; Hao-Ru ZHANG ² ; Zhi-Long JIANG ¹ ; Yan-Zhong CHANG ² ; Chang-Zhou SHAO ¹
Author Information

1. Department of Pulmonary Medicine, Shanghai Institute of Respiratory Diseases, Zhongshan Hospital, Fudan University, Shanghai 200032, China.
2. Laboratory of Molecular Iron Metabolism, The Key Laboratory of Animal Physiology, Biochemistry and Molecular Biology of Hebei Province, College of Life Science, Hebei Normal University, Shijiazhuang, Hebei 050024, China.
Publication Type:Journal Article
Keywords: Asepergillus fumigatus; Dendritic Cell-Specific Intercellular Adhesion Molecule-3-Grabbing Nonintegrin; Dendritic Cells; Immunity
From: Chinese Medical Journal 2018;131(21):2575-2582
CountryChina
Language:English
Abstract:
BackgroundDendritic 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.
MethodsDCs were first obtained from the mononuclear cells of peripheral blood. The interferon (IFN)-γ 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)-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.
ResultsExogenous IFN-γ could activate Af-induced DCs and promote the Th0 cells toward Th1 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/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-κB activation.
ConclusionOverexpressing DC-SIGN in DCs had a protective function on aspergillosis.