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3型分泌系统识别控制的独特机制 LTB₄ 中性粒细胞与巨细胞的合成

Amanda Brady¹, Leonardo C Mora-Martinez¹, Benjamin Hammond¹

¹Department of Microbiology and Immunology, University of Louisville School of Medicine, Louisville, Kentucky, United States of America.

bioRxiv : the preprint server for biology

|July 15, 2024

概括

细菌3型分泌系统 (T3SS) 触发了白血素B4 (LTB) 的产生,但Yersinia抑制了它. 中性粒细胞和巨细胞在感染期间使用不同的路径合成LTB.

科学领域:

免疫学免疫学免疫学
微生物学微生物学
细胞生物学细胞生物学

背景情况:

列可特里因B4 (LTB) 是感染期间炎症的关键媒介.
病原性细菌,如Yersinia pestis,可以通过破坏炎症信号来逃避免疫反应.
细菌3型分泌系统 (T3SS) 是一个关键的毒性因素.

研究的目的:

阐明T3SS在启动白细胞LTB₄产生中的作用.
确定中性粒细胞和巨细胞用于T3SS介导的LTB合成的独特宿主信号通路.
要了解Yersinia pestis的Yop效应物如何抑制LTB的产生.

主要方法:

研究了对表达T3SS的细菌 (Yersinia和Salmonella) 的反应中的LTB₄产生.
利用遗传学和药理学方法来剖析宿主信号通路 (SKAP2 / PLC,细胞化,NLRP3 / CASP1炎症体,MAP激酶).
中性粒细胞与巨细胞的不同信号要求.

主要成果:

T3SS作为一种与病原体相关的分子模式 (PAMP),诱导白细胞中的LTB₄生产.
耶尔西尼亚效应剂抑制T3SS介导的LTB合成.
中性细胞LTB₄的产生需要SKAP2/PLC路径.
巨细胞LTB₄的合成取决于细胞和NLRP3/CASP1炎症体.
第二个独立的PAMP信号激活了MAP激酶,用于LTB合成.

结论:

响应T3SS的白细胞LTB₄生产在中性粒细胞和巨细胞中受到差异调节.
显著的细胞内信号级联控制LTB₄合成,以应对细菌PAMPs.
了解这些途径可以了解宿主-病原体相互作用和免疫逃避策略.

关键词:

这就是T3SS.耶尔西尼亚瘟疫 (Yersinia pestis) 是一种传染病.这是一种炎症炎症炎症炎症.莱克托里因B4 B4的使用专业的细胞.

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