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Galactosaminogalactan 激活炎症酶以提供宿主保护

Benoit Briard¹, Thierry Fontaine², Parimal Samir¹

¹Department of Immunology, St Jude Children's Research Hospital, Memphis, TN, USA.

|December 3, 2020

概括

作为一种与病原体相关的分子模式 (PAMP),Aspergillus fumigatus galactosaminogalactan通过与核糖体蛋白结合来激活NLRP3炎症体. 这一发现揭示了与生俱来的免疫防御机制,

科学领域:

免疫学
微生物学
分子生物学

背景情况:

炎症体是由病原体相关分子模式 (PAMPs) 激活的重要先天免疫哨兵.
炎症酶激活为宿主提供了对Aspergillus fumigatus的防御,这是对免疫功能低下的个体的重大威胁.
触发炎酶激活的Aspergillus fumigatus特定的PAMP仍未确定.

研究的目的:

为了识别负责炎症酶激活的Aspergillus fumigatus PAMP.
阐明这种PAMP激活NLRP3炎症体的机制.
研究这种PAMP在宿主防御和潜在的治疗应用中的作用.

主要方法:

鉴定银胺类银素 (GAG) 是一种Aspergillus fumigatus的PAMP.
证明GAG与核糖体蛋白结合并抑制细胞翻译.
对GAG反应的炎症酶激活的评估.
在小鼠模型中评估GAG缺乏阿斯伯吉勒斯突变的毒性.
在牛硫酸盐诱导的大肠炎小鼠模型中测试GAG的疗效.

主要成果:

Aspergillus fumigatus galactosaminogalactan (GAG) 被确定为一种激活NLRP3炎症体的PAMP.
GAG与核糖体蛋白质结合,抑制细胞翻译,随后激活NLRP3炎症体.
一种GAG缺乏的Aspergillus突变呈现出增加的毒性,并且未能在小鼠中引起保护性炎症酶激活.
用GAG证明了对硫酸诱导的大肠炎的保护作用,这种作用依赖于炎症体.

结论:

核糖体是真菌PAMP GAG的感知和先天免疫反应的激活之间的关键环节.
GAG是Aspergillus fumigatus的一个关键的PAMP,通过核糖体抑制触发炎症酶激活.
这一发现为真菌识别机制和潜在的治疗策略提供了新的见解.

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