人类单细胞细胞因超病毒性Streptococcus pyogenes感染而减少了互白素-18的分泌
Lea A Tölken1, Antje D Paulikat1, Lana H Jachmann1
1Department of Molecular Genetics and Infection Biology, University of Greifswald, Greifswald, Germany.
Journal of biomedical science
|February 26, 2024
概括
在Streptococcus pyogenes covR/S基因中的突变会减少免疫细胞释放的IL-8和IL-18. 这种对宿主反应的干扰可能会导致严重的死软组织感染 (NSTI).
科学领域:
- 免疫学 免疫学 免疫学
- 微生物学 微生物学
- 传染性疾病 传染性疾病
背景情况:
- 杆菌 pyogenes (GAS) 引起各种感染,从轻微到严重的死菌软组织感染 (NSTI).
- 由于CovR/S两组系统的突变,GAS的毒性可能会增加,导致超级毒性.
- 树突细胞 (DCs) 是启动T细胞反应的关键免疫细胞.
研究的目的:
- 研究野生型和covR/S突变GAS菌株如何影响树突细胞 (DC) 和其他单细胞细胞的细胞因子释放.
- 分析GAS covR/S突变对先天免疫反应的影响.
主要方法:
- 人类初级单细胞衍生的树突细胞 (moDCs) 被野生型和covR/S突变GAS菌株感染.
- 细胞因子释放和DC成熟被评估使用流动细胞计.
- 全球蛋白质组变化通过质谱分析;从单细胞和巨细胞释放的细胞因子也被测试.
主要成果:
- 与野生型菌株相比,GAS covR/S突变诱导了moDC和其他单细胞细胞中IL-8和IL-18的分泌量较低.
- 突变没有影响DC成熟; caspase-8抑制恢复了IL-8和IL-18的分泌.
- 虽然67个NSTI GAS分离体中的28个具有功能障碍的CovR/S,但血IL-8和IL-18水平与这些突变无关.
结论:
- 具有covR/S突变的GAS菌株通过caspase-8通路损害单细胞中的IL-18和IL-8反应.
- 这些发现表明,GAS可以通过一种机制逃避免疫检测,从而可能导致NSTI的严重程度.
- 需要进一步的研究来阐明NSTI患者的确切机制和临床影响.
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