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来自申克孢子丝菌的富含几丁质的杂多糖增强了孢子丝菌病小鼠模型中的真菌清除能力,并促进了巨噬细胞的吞噬作用。

Chitin-rich heteroglycan from Sporothrix schenckii sensu stricto potentiates fungal clearance in a mouse model of sporotrichosis and promotes macrophages phagocytosis.

机构信息

Department of Dermatology and Venereology, The Third Affiliated Hospital of Sun Yat-Sen University, 600# Tianhe Road, Guangzhou, 510630, China.

Department of Pediatrics, Guangdong Women and Children Hospital, Guangzhou, China.

出版信息

BMC Microbiol. 2021 Jun 25;21(1):190. doi: 10.1186/s12866-021-02243-w.

DOI:10.1186/s12866-021-02243-w
PMID:34171998
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC8228915/
Abstract

BACKGROUND

Fungal cell wall polysaccharides maintain the integrity of fungi and interact with host immune cells. The immunomodulation of fungal polysaccharides has been demonstrated in previous studies. However, the effect of chitin-rich heteroglycan extracted from Sporothrix schenckii sensu stricto on the immune response has not been investigated.

RESULTS

In this study, chitin-rich heteroglycan was extracted from S. schenckii sensu stricto, and immunomodulation was investigated via histopathological analysis of skin lesions in a mouse model of sporotrichosis and evaluation of the phagocytic function and cytokine secretion of macrophages in vitro. The results showed that the skin lesions regressed and granulomatous inflammation was reduced in infected mice within 5 weeks. Moreover, heteroglycan promoted the fungal phagocytosis by macrophages and modulated the cytokine secretion. Heteroglycan upregulated TNF-α expression early at 24 h and IL-12 expression late at 72 h after incubation, which might result from moderate activation of macrophages and contribute to the subsequent adaptive immune response.

CONCLUSIONS

Chitin-rich heteroglycan extracted from S. schenckii sensu stricto potentiated fungal clearance in a mouse model of sporotrichosis. Moreover, chitin-rich heteroglycan promoted fungus phagocytosis by macrophages and modulated cytokines secretion. These results might indicate that chitin-rich heteroglycan could be considered as an immunomodulator used in the treatment of sporotrichosis.

摘要

背景

真菌细胞壁多糖维持真菌的完整性,并与宿主免疫细胞相互作用。真菌多糖的免疫调节作用已在先前的研究中得到证实。然而,从严格意义上的申克孢子丝菌中提取的富含几丁质的杂聚糖对免疫反应的影响尚未得到研究。

结果

本研究从严格意义上的申克孢子丝菌中提取了富含几丁质的杂聚糖,并通过对孢子丝菌病小鼠模型皮肤损伤的组织病理学分析以及体外评估巨噬细胞的吞噬功能和细胞因子分泌来研究其免疫调节作用。结果表明,在感染后的 5 周内,感染小鼠的皮肤损伤消退,肉芽肿性炎症减轻。此外,杂聚糖促进了巨噬细胞对真菌的吞噬作用,并调节了细胞因子的分泌。杂聚糖在孵育 24 小时时上调 TNF-α 的表达,在孵育 72 小时时上调 IL-12 的表达,这可能是由于巨噬细胞的适度激活,并有助于随后的适应性免疫反应。

结论

从严格意义上的申克孢子丝菌中提取的富含几丁质的杂聚糖增强了孢子丝菌病小鼠模型中的真菌清除能力。此外,富含几丁质的杂聚糖促进了巨噬细胞对真菌的吞噬作用,并调节了细胞因子的分泌。这些结果可能表明,富含几丁质的杂聚糖可用作孢子丝菌病治疗的免疫调节剂。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/9ef9/8228915/a9158891d2cc/12866_2021_2243_Fig5_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/9ef9/8228915/e3917a6ad26c/12866_2021_2243_Fig1_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/9ef9/8228915/449a193da302/12866_2021_2243_Fig2_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/9ef9/8228915/f14acf86521f/12866_2021_2243_Fig3_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/9ef9/8228915/652d8c6fc827/12866_2021_2243_Fig4_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/9ef9/8228915/a9158891d2cc/12866_2021_2243_Fig5_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/9ef9/8228915/e3917a6ad26c/12866_2021_2243_Fig1_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/9ef9/8228915/449a193da302/12866_2021_2243_Fig2_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/9ef9/8228915/f14acf86521f/12866_2021_2243_Fig3_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/9ef9/8228915/652d8c6fc827/12866_2021_2243_Fig4_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/9ef9/8228915/a9158891d2cc/12866_2021_2243_Fig5_HTML.jpg

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