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与来自对屋尘螨过敏患者的产生白细胞介素-18的卡介苗脉冲树突状细胞共培养的初始T细胞产生白细胞介素-5减少。

Decrease of IL-5 Production by Naive T Cells Cocultured with IL-18-Producing BCG-Pulsed Dendritic Cells from Patients Allergic to House Dust Mite.

作者信息

Kowalewicz-Kulbat Magdalena, Szpakowski Piotr, Krawczyk Krzysztof T, Kowalski Marek L, Kosinski Slawomir, Biet Franck, Rudnicka Wieslawa, Locht Camille

机构信息

Department of Immunology and Infectious Biology, Institute of Microbiology, Biotechnology and Immunology, Faculty of Biology and Environmental Protection, University of Lodz, 90-237 Lodz, Poland.

Department of Neurology and Stroke, Medical University of Lodz, 90-549 Lodz, Poland.

出版信息

Vaccines (Basel). 2021 Mar 18;9(3):277. doi: 10.3390/vaccines9030277.

Abstract

The only currently available anti-tuberculosis vaccine, Bacillus Calmette-Guérin (BCG), has been reported to also protect against unrelated diseases, including inflammatory diseases such as allergic asthma. Recombinant BCG strains that produce IL-18 have been shown to enhance Th1 responses over non-recombinant BCG and to reduce IL-5 production and bronchoalveolar eosinophilia in mice. However, their ability to decrease the immune polarization of human Th2 cells is not known. Here, we show that BCG and recombinant BCG producing human IL-18 (rBCG-hIL-18) induced the maturation of Der p 1-stimulated monocyte-derived dendritic cells (MD-DCs) from healthy controls and from patients allergic to house dust mites. After incubation with mycobacteria and Der p 1, MD-DCs produced significantly more IL-23 and IP-10 but had no effect on IL-12p70 or IL-10 production compared to Der p 1-pulsed MD-DCs in the absence of mycobacteria. In the presence of Der p 1, BCG- and rBCG-hIL-18-pulsed MD-DCs cocultured with naive, but not with memory T cells from allergic patients, resulted in a decrease in IL-5 production compared to non-pulsed MD-DCs cultured in the presence of Der p 1. BCG, and especially rBCG-hIL-18, may thus be potential therapeutic tools to reduce exacerbated Th2 responses in patients with allergic asthma.

摘要

目前唯一可用的抗结核疫苗卡介苗(BCG),据报道还能预防不相关疾病,包括过敏性哮喘等炎症性疾病。已证明产生IL-18的重组卡介苗菌株比非重组卡介苗能增强Th1反应,并减少小鼠体内IL-5的产生和支气管肺泡嗜酸性粒细胞增多。然而,它们降低人类Th2细胞免疫极化的能力尚不清楚。在此,我们表明卡介苗和产生人IL-18的重组卡介苗(rBCG-hIL-18)可诱导来自健康对照者和对屋尘螨过敏患者的Der p 1刺激的单核细胞衍生树突状细胞(MD-DC)成熟。与在无分枝杆菌情况下Der p 1脉冲处理的MD-DC相比,在与分枝杆菌和Der p 1孵育后,MD-DC产生的IL-23和IP-10显著增多,但对IL-12p70或IL-10的产生没有影响。在存在Der p 1的情况下,与来自过敏患者的记忆T细胞共培养时,卡介苗和rBCG-hIL-18脉冲处理的MD-DC与未致敏T细胞共培养,与在Der p 1存在下培养的未脉冲处理的MD-DC相比,导致IL-5产生减少。因此,卡介苗,尤其是rBCG-hIL-18,可能是减少过敏性哮喘患者Th2反应加剧的潜在治疗工具。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/df1e/8003153/2b7e4ee11bee/vaccines-09-00277-g001.jpg

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