Tang Yanping, Zhang Hui, Xu Haiguang, Zeng Wen, Qiu Ye, Tan Caimei, Tang Shudan, Zhang Jianquan
Department of Respiratory and Critical Care Medicine, The First Affiliated Hospital of Guangxi Medical University, Nanning, Guangxi, People's Republic of China.
Infect Drug Resist. 2020 Mar 11;13:805-813. doi: 10.2147/IDR.S239906. eCollection 2020.
Dendritic cells (DCs) with both proinflammatory and tolerogenic properties have been implicated in modulation of CD4 T cell responses in many fungal diseases. However, the role of DC in the context of () infection has not been determined. In this study, we aimed to study the effect of the yeast form of yeasts on DCs, as well as the role of DCs in modulating T helper 17 (Th17) and regulatory T (Treg) cell responses to the pathogen.
Mouse bone marrow-derived DCs were stimulated with yeasts for 24 h. Frequencies of CD80 and CD86 expression on DCs and the levels of IL-6, IL-10 and TGF-β in the culture supernatant of yeast-stimulated DCs were detected by flow cytometry and ELISA, respectively. In co-culture experiments, CD4 T lymphocytes of mice were isolated from the spleen using magnetic beads and co-cultured with yeasts, with or without DCs for 24 h. The proportions of Th17 and Treg cells in co-culture were detected by flow cytometry. The mRNA levels of and were detected by RT-PCR. Levels of IL-10 and TGF-β in the co-culture supernatant were detected by ELISA.
The expressions of CD80 and CD86 on DCs were increased, as well as IL-6, IL-10 and TGF-β levels in the culture supernatant of -stimulated DCs were higher than those in DCs cultured without . In co-culture experiments, in the presence of DCs, promoted Treg expansion and Foxp3 up-regulation but limited Th17 and downregulated RORγt. Levels of IL-10 and TGF-β were higher in the co-culture containing DCs than without DCs.
Our findings demonstrated that the interaction between DCs and could promote Treg expansion but not Th17 generation. These findings provide a mechanism by which DCs may promote immune tolerance in infection.
具有促炎和致耐受性特性的树突状细胞（DCs）在许多真菌疾病中参与调节CD4 T细胞反应。然而，DC在（）感染情况下的作用尚未确定。在本研究中，我们旨在研究酵母形式的酵母对DCs的影响，以及DCs在调节T辅助细胞17（Th17）和调节性T（Treg）细胞对病原体反应中的作用。
用酵母刺激小鼠骨髓来源的DCs 24小时。分别通过流式细胞术和酶联免疫吸附测定法检测DCs上CD80和CD86的表达频率以及酵母刺激的DCs培养上清液中IL-6、IL-10和TGF-β的水平。在共培养实验中，使用磁珠从脾脏中分离小鼠的CD4 T淋巴细胞，并与酵母共培养24小时，有或没有DCs。通过流式细胞术检测共培养中Th17和Treg细胞的比例。通过逆转录聚合酶链反应检测和的mRNA水平。通过酶联免疫吸附测定法检测共培养上清液中IL-10和TGF-β的水平。
DCs上CD80和CD86的表达增加，并且刺激的DCs培养上清液中IL-6、IL-10和TGF-β水平高于未培养的DCs。在共培养实验中，在存在DCs的情况下，促进了Treg扩增和Foxp3上调，但限制了Th17并下调了RORγt。含有DCs的共培养中IL-10和TGF-β水平高于没有DCs的共培养。
我们的研究结果表明，DCs与之间的相互作用可促进Treg扩增，但不能促进Th17生成。这些发现提供了一种机制，通过该机制DCs可能在感染中促进免疫耐受。
