呼吸道粘膜中的中性炎症会导致RSV感染
Maximillian S Habibi1, Ryan S Thwaites1, Meiping Chang2
1National Heart and Lung Institute, Imperial College London, London, UK.
概括
在呼吸道同胞病毒 (RSV) 暴露之前的粘膜中性粒细胞激活预示着症状性疾病. 早期的免疫媒介变化,而不是基线微生物组,决定了感染结果,为病毒易感性提供了新的见解.
科学领域:
- 免疫学
- 病毒学
- 呼吸系统医学
背景情况:
- 呼吸道同胞病毒 (RSV) 等病毒感染后的结果的变异性尚未完全理解.
- 已知因素不能完全解释为什么有些人会患上严重的疾病,而另一些人则保持无症状或抵抗感染.
研究的目的:
- 调查呼吸道同胞病毒 (RSV) 暴露前存在的免疫因素,从而预测疾病的结果.
- 为了阐明与RSV感染的易感性或耐药性相关的早期症状前免疫反应.
主要方法:
- 对58名志愿者进行呼吸道同胞病毒 (RSV) 治疗.
- 在感染前和感染期间监测粘膜免疫媒介和中性粒细胞激活.
- 利用小鼠模型研究中性粒细胞招募和随后免疫细胞透在疾病发病中的作用.
主要成果:
- 57% 的志愿者感染了RSV.
- 暴露前的粘膜中性粒细胞激活强烈预测了症状性RSV疾病.
- 有症状的个体表现出interleukin- 17A (IL- 17A) 和其他调解剂的预症状下降.
- 耐药个体表现出IL-17和瘤亡因子通路的预症状激活.
- 基线微生物组与感染脆弱性没有相关性.
- 通过CD8+T细胞透,中性细胞在小鼠中增加导致疾病的增强.
结论:
- 在RSV暴露时的粘膜中性炎症增加了感染和疾病的易感性.
- 在症状出现之前发生的动态的,依赖时间的局部免疫反应对于确定病毒感染结果至关重要.
- 这些发现为以前无法预测的病原体暴露反应的变异性提供了新的解释.
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