Listeria toxin promotes phosphorylation of the inflammasome adaptor ASC through Lyn and Syk to exacerbate pathogen expansion
Listeria toxin promotes phosphorylation of the inflammasome adaptor ASC through Lyn and Syk to exacerbate pathogen expansion
复制标题
李斯特菌毒素通过 Lyn 和 Syk 促进炎症小体接头 ASC 磷酸化，从而加剧病原体扩张
DOI：
10.1016/j.celrep.2022.110414
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发表时间：
2022
期刊：
影响因子：
8.8
通讯作者：
Hara Hideki
中科院分区：
文献类型：
--
作者：
Tanishita Yuko;Sekiya Hisateru;Inohara Naohiro;Tsuchiya Kohsuke;Mitsuyama Masao;Nunez Gabriel;Hara Hideki
炎性小体激活会加重由病原体如单核细胞增生李斯特菌、金黄色葡萄球菌和严重急性呼吸综合征冠状病毒2引起的感染性疾病。虽然这些病原体激活宿主炎性小体来调节病原体的扩张，但病原体毒素促进炎性小体激活的机制仍然知之甚少。在这里，我们表明，李斯特菌感染的炎性小体的激活是促进氨基酸残基T223的溶血素O（LLO）独立的孔形成活性。LL 0 T223通过Lyn-Syk信号传导对炎性小体衔接子ASC在氨基酸残基Y144处的磷酸化至关重要，这对于ASC寡聚化是必需的。值得注意的是，表达LLO T223 A的李斯特菌在诱导ASC磷酸化和炎性小体活化方面受损。此外，LLO T223 A突变体的毒力由于激活炎性小体的能力受损而在体内显著减弱。我们的研究结果揭示了病原体毒素通过促进ASC的磷酸化而加剧感染的功能。
Inflammasome activation exacerbates infectious disease caused by pathogens such asListeria monocytogenes,Staphylococcus aureus, and severe acute respiratory syndrome coronavirus 2. Although these pathogens activate host inflammasomes to regulate pathogen expansion, the mechanisms by which pathogen toxins contribute to inflammasome activation remain poorly understood. Here we show that activation of inflammasomes byListeriainfection is promoted by amino acid residue T223 of listeriolysin O (LLO) independently of its pore-forming activity. LLO T223 is critical for phosphorylation of the inflammasome adaptor ASC at amino acid residue Y144 through Lyn-Syk signaling, which is essential for ASC oligomerization. Notably, aListeriamutant expressing LLO T223A is impaired in inducing ASC phosphorylation and inflammasome activation. Furthermore, the virulence of LLO T223A mutant is markedly attenuatedin vivodue to impaired ability to activate the inflammasome. Our results reveal a function of a pathogen toxin that exacerbates infection by promoting phosphorylation of ASC.