PMID- 30381591 OWN - NLM STAT- MEDLINE DCOM- 20190226 LR - 20220321 IS - 2542-5641 (Electronic) IS - 0366-6999 (Print) IS - 0366-6999 (Linking) VI - 131 IP - 21 DP - 2018 Nov 5 TI - Overexpression of Dendritic Cell-Specific Intercellular Adhesion Molecule-3-Grabbing Nonintegrin in Dendritic Cells Protecting against Aspergillosis. PG - 2575-2582 LID - 10.4103/0366-6999.244103 [doi] AB - 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)-gamma 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)-kappaB 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-gamma could activate Af-induced DCs and promote the Th0 cells toward Th1 profile (interleukin [IL]-12 in IFN-gamma/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-kappaB activation. CONCLUSION: Overexpressing DC-SIGN in DCs had a protective function on aspergillosis. FAU - Li, Li-Yang AU - Li LY AD - Department of Pulmonary Medicine, Shanghai Institute of Respiratory Diseases, Zhongshan Hospital, Fudan University, Shanghai 200032, China. FAU - Zhang, Hao-Ru AU - Zhang HR AD - 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. FAU - Jiang, Zhi-Long AU - Jiang ZL AD - Department of Pulmonary Medicine, Shanghai Institute of Respiratory Diseases, Zhongshan Hospital, Fudan University, Shanghai 200032, China. FAU - Chang, Yan-Zhong AU - Chang YZ AD - 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. FAU - Shao, Chang-Zhou AU - Shao CZ AD - Department of Pulmonary Medicine, Shanghai Institute of Respiratory Diseases, Zhongshan Hospital, Fudan University, Shanghai 200032, China. LA - eng PT - Journal Article PL - China TA - Chin Med J (Engl) JT - Chinese medical journal JID - 7513795 RN - 0 (Cell Adhesion Molecules) RN - 0 (DC-specific ICAM-3 grabbing nonintegrin) RN - 0 (Lectins, C-Type) RN - 0 (NF-kappa B) RN - 0 (Receptors, Cell Surface) RN - 7S5I7G3JQL (Dexamethasone) RN - 82115-62-6 (Interferon-gamma) SB - IM MH - Aspergillosis/immunology/*metabolism MH - Aspergillus fumigatus/pathogenicity MH - Cell Adhesion Molecules/*metabolism MH - Cells, Cultured MH - Dendritic Cells/*metabolism MH - Dexamethasone/pharmacology MH - Humans MH - Immunosuppression Therapy MH - Immunotherapy MH - Interferon-gamma/pharmacology MH - Lectins, C-Type/*metabolism MH - NF-kappa B/metabolism MH - Receptors, Cell Surface/*metabolism MH - Th1 Cells/immunology/metabolism MH - Th2 Cells/immunology/metabolism PMC - PMC6213851 OTO - NOTNLM OT - Asepergillus fumigatus OT - Dendritic Cell-Specific Intercellular Adhesion Molecule-3-Grabbing Nonintegrin OT - Dendritic Cells OT - Immunity COIS- There are no conflicts of interest EDAT- 2018/11/02 06:00 MHDA- 2019/02/27 06:00 PMCR- 2018/11/05 CRDT- 2018/11/02 06:00 PHST- 2018/11/02 06:00 [entrez] PHST- 2018/11/02 06:00 [pubmed] PHST- 2019/02/27 06:00 [medline] PHST- 2018/11/05 00:00 [pmc-release] AID - ChinMedJ_2018_131_21_2575_244103 [pii] AID - CMJ-131-2575 [pii] AID - 10.4103/0366-6999.244103 [doi] PST - ppublish SO - Chin Med J (Engl). 2018 Nov 5;131(21):2575-2582. doi: 10.4103/0366-6999.244103.