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金黄色葡萄球菌通过STING在伴鼻息肉的慢性嗜酸性粒细胞性鼻窦炎中调节Th17细胞和自噬。

Staphylococcus aureus regulates Th17 cells and autophagy via STING in chronic eosinophilic rhinosinusitis with nasal polyps.

作者信息

Gan Weigang, Liu Xingchen, Liu Feng, Hu Junying

机构信息

Department of Otolaryngology Head and Neck Surgery, West China Hospital of Sichuan University, Sichuan Province, 37Guoxue Lane, Chengdu, 610041, China.

出版信息

Eur Arch Otorhinolaryngol. 2025 Feb;282(2):881-894. doi: 10.1007/s00405-024-09100-2. Epub 2024 Dec 14.

DOI:10.1007/s00405-024-09100-2
PMID:39674846
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC11805884/
Abstract

PURPOSE

As a common pathogen of rhinosinusitis, the role of Staphylococcus aureus in modulating autophagy through STING activation and Th17 cell differentiation in CRSwNP remains unexplored. This study aims to investigate how S. aureus regulates Th17 cell differentiation and the occurrence and development of autophagy in CRS by inducing STING expression.

METHODS

Immunoblotting and flow cytometry were employed to assess the expression levels of STING, RORγt, LC3B, and MUC5AC, as well as Th17 markers in cells. HNECs were co-cultured with S. aureus in vitro to explore its regulatory effects.

RESULTS

STING expression was found to be decreased in CRSwNP tissues, while RORγt, LC3B, and MUC5AC levels were elevated. S. aureus was shown to induce Th17 differentiation via STING regulation. STING activators reduced Th17 inflammation, while autophagy activators increased autophagosomes and MUC5AC levels.

CONCLUSION

The STING system may play a protective role in the inflammatory response of nasal epithelial cells. S. aureus inhibits STING, not only by promoting the differentiation of pathogenic Th17 cells but also by increasing autophagy levels in nasal epithelial cells. Both mechanisms contribute to the enhanced expression of MUC5AC, facilitating the progression of CRSwNP.

摘要

目的

金黄色葡萄球菌作为鼻窦炎的常见病原体,其在慢性鼻-鼻窦炎伴鼻息肉(CRSwNP)中通过刺激干扰素基因刺激蛋白(STING)激活和辅助性T细胞17(Th17)细胞分化来调节自噬的作用仍未得到探索。本研究旨在探讨金黄色葡萄球菌如何通过诱导STING表达来调节CRS中Th17细胞分化以及自噬的发生和发展。

方法

采用免疫印迹法和流式细胞术评估细胞中STING、维甲酸相关孤儿受体γt(RORγt)、微管相关蛋白1轻链3β(LC3B)和黏蛋白5AC(MUC5AC)的表达水平,以及Th17标志物。体外将人鼻上皮细胞(HNECs)与金黄色葡萄球菌共培养,以探讨其调节作用。

结果

发现CRSwNP组织中STING表达降低,而RORγt、LC3B和MUC5AC水平升高。金黄色葡萄球菌被证明可通过STING调节诱导Th17分化。STING激活剂可减轻Th17炎症,而自噬激活剂可增加自噬体和MUC5AC水平。

结论

STING系统可能在鼻上皮细胞的炎症反应中起保护作用。金黄色葡萄球菌抑制STING,不仅通过促进致病性Th17细胞的分化,还通过增加鼻上皮细胞中的自噬水平。这两种机制都有助于MUC5AC表达的增强,促进CRSwNP的进展。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/8d51/11805884/e210e825a23b/405_2024_9100_Fig6_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/8d51/11805884/a9d437107339/405_2024_9100_Fig1_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/8d51/11805884/66172377028c/405_2024_9100_Fig2_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/8d51/11805884/993d6d2453de/405_2024_9100_Fig3_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/8d51/11805884/8a483043c369/405_2024_9100_Fig4_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/8d51/11805884/a45d3d5d841a/405_2024_9100_Fig5_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/8d51/11805884/e210e825a23b/405_2024_9100_Fig6_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/8d51/11805884/a9d437107339/405_2024_9100_Fig1_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/8d51/11805884/66172377028c/405_2024_9100_Fig2_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/8d51/11805884/993d6d2453de/405_2024_9100_Fig3_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/8d51/11805884/8a483043c369/405_2024_9100_Fig4_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/8d51/11805884/a45d3d5d841a/405_2024_9100_Fig5_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/8d51/11805884/e210e825a23b/405_2024_9100_Fig6_HTML.jpg

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本文引用的文献

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Neutrophils Play an Important Role in the Recurrence of Chronic Rhinosinusitis with Nasal Polyps.中性粒细胞在伴鼻息肉的慢性鼻-鼻窦炎复发中起重要作用。
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Beyond autophagy: LC3-associated phagocytosis and endocytosis.
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STING is an intrinsic checkpoint inhibitor that restrains the T17 cell pathogenic program.STING 是一种内在的检查点抑制剂,它抑制 T17 细胞的致病程序。
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The cGAS-STING Pathway in Bacterial Infection and Bacterial Immunity.cGAS-STING 通路在细菌感染和细菌免疫中的作用。
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