Dendritic Cells Promote Treg Expansion but Not Th17 Generation in Response to Talaromyces marneffei Yeast Cells
Dendritic Cells Promote Treg Expansion but Not Th17 Generation in Response to Talaromyces marneffei Yeast Cells
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DOI：
10.2147/idr.s239906
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发表时间：
2020-03
影响因子：
3.9
通讯作者：
Yanping Tang;Hui Zhang;Haiguang Xu;W. Zeng;Y. Qiu;C. Tan;Shudan Tang;Jianquan Zhang
中科院分区：
文献类型：
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作者：
Yanping Tang;Hui Zhang;Haiguang Xu;W. Zeng;Y. Qiu;C. Tan;Shudan Tang;Jianquan Zhang
背景树突状细胞（Dendritic cells，DCs）具有促炎和致耐受特性，在许多真菌疾病中参与调节CD 4 + T细胞应答。然而，DC在Talaromyces marneffei（T. marneffei）感染尚未确定。在这项研究中，我们的目的是研究的影响，酵母形式的T。马尔尼菲酵母对DC的作用，以及DC在调节T辅助17（Th 17）和调节性T（Treg）细胞对病原体的应答中的作用。方法用T.马尔尼菲酵母24小时。流式细胞术检测DC表面CD 80和CD 86的表达，ELISA检测酵母刺激DC培养上清中IL-6、IL-10和TGF-β的水平。在共培养实验中，用磁珠法从小鼠脾脏中分离CD 4 + T淋巴细胞，并与T淋巴细胞共培养。马尔尼菲酵母，有或没有DC的24小时。流式细胞仪检测共培养物中Th 17和Treg细胞的比例。RT-PCR检测RORγt和Foxp 3 mRNA水平。ELISA法检测共培养上清中IL-10和TGF-β的水平。结果T淋巴细胞培养上清中IL-6、IL-10和TGF-β的水平明显升高，DC表面CD 80和CD 86的表达明显增加。marneffei刺激的DCs比无T.马尔尼菲酒。在共培养实验中，在DC存在下，T. marneffei促进Treg扩增和Foxp 3上调，但限制Th 17，下调RORγt。含DC的共培养物中IL-10和TGF-β的水平高于不含DC的共培养物。结论DCs与T淋巴细胞的相互作用可能与T淋巴细胞的增殖有关。marneffei能促进Treg扩增，但不能促进Th 17的产生。这些发现提供了一种机制，通过这种机制，DC可能促进T细胞的免疫耐受。马尔尼菲感染。
Background 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 Talaromyces marneffei (T. marneffei) infection has not been determined. In this study, we aimed to study the effect of the yeast form of T. marneffei 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. Methods Mouse bone marrow-derived DCs were stimulated with T. marneffei 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 T. marneffei 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 RORγt and Foxp3 were detected by RT-PCR. Levels of IL-10 and TGF-β in the co-culture supernatant were detected by ELISA. Results 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 T. marneffei-stimulated DCs were higher than those in DCs cultured without T. marneffei. In co-culture experiments, in the presence of DCs, T. marneffei 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. Conclusion Our findings demonstrated that the interaction between DCs and T. marneffei could promote Treg expansion but not Th17 generation. These findings provide a mechanism by which DCs may promote immune tolerance in T. marneffei infection.