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人类STING基因型和细菌NADase活性之间的相互作用调节了个体之间的疾病变异性

Elin Movert¹, Jaume Salgado Bolarin¹, Christine Valfridsson¹

¹Department of Biology, Lund University, Sölvegatan 35, 223 62, Lund, Sweden.

Nature communications

|July 6, 2023

概括

主体STING基因型和Streptococcus pyogenes NADase活性决定了侵入性感染的结果. 减少STING结合加上高细菌NADase活性导致严重的疾病,而强大的STING反应提供了保护.

科学领域:

微生物学微生物学
免疫学免疫学免疫学
遗传学是一个遗传学.

背景情况:

侵袭性Streptococcus pyogenes感染由于宿主-病原体遗传相互作用而表现出不同的严重程度.
STING通路和I型干扰素 (IFN) 反应对抗细菌病原体的先天免疫是至关重要的.

研究的目的:

研究人类STING基因型和细菌NADase活性在调节侵入性Streptococcus pyogenes感染结果中的相互作用.
阐明细菌NADase影响宿主免疫反应的机制.

主要方法:

分析Streptococcus pyogenes衍生的循环二-AMP (c-di-AMP) 通过Streptolysin O孔隙的扩散.
在巨细胞中评估STING激活和I型IFN产生.
在患有死性S. pyogenes感染的患者中,STING的基因定型.
细菌NADase活性与患者结果的相关性.

主要成果:

细菌c-di-AMP通过链条素O孔激活STING和I型IFN反应.
细菌的NADase活性抑制了STING介导的I型IFN生产.
具有降低c-di-AMP结合能力的特定STING基因型,加上高的细菌NADase活性,与死感染患者的不良结果相关.

结论:

细菌NADase具有免疫调节功能,抑制宿主I型IFN反应.
主体STING基因型和细菌NADase活性之间的相互作用是侵入性Streptococcus pyogenes感染严重程度和个体间变异性的关键决定因素.
了解这种宿主-病原体基因型相互作用,可以深入了解疾病病原体和潜在的治疗点.

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