人类IRF1控制着对真菌菌的巨性IFN-γ免疫力
Jérémie Rosain1, Anna-Lena Neehus2, Jérémy Manry3
1Laboratory of Human Genetics of Infectious Diseases, Inserm U1163, 75015 Paris, France; Paris Cité University, Imagine Institute, 75015 Paris, France.
Cell
|February 3, 2023
概括
遗传的IRF1缺陷会导致严重的菌根性疾病,而不是病毒感染. IRF1对于IFN-γ驱动的免疫是至关重要的,但对于IFN-α/β驱动的抗病毒防御则不那么重要.
科学领域:
- 免疫学
- 人类遗传学
- 传染性疾病
背景情况:
- 干扰素- (IFN-γ) 依赖免疫的先天性错误导致菌根性疾病.
- 与干扰素α/β (IFN-α/β) 相关的免疫系统的先天性错误导致病毒性疾病.
- 两种IFN-γ和IFN-α/β都诱导了转录因子干扰素调节因子1 (IRF1).
研究的目的:
- 研究IRF1在人类免疫中的作用.
- 描述遗传IRF1缺陷的临床和免疫特征.
主要方法:
- 描述的非亲属儿童具有遗传的完整IRF1缺陷.
- 在白细胞和纤维细胞中评估了对IFN-γ和IFN-α/β的IRF1依赖反应.
- 在IRF1缺乏的细胞中对菌根和病毒进行了评估.
主要成果:
- 患有IRF1缺乏症的儿童患有危及生命的菌根性疾病,但没有严重的病毒感染.
- 对IFN-γ的IRF1依赖反应在体外比对IFN-α/β更强.
- 缺少IRF1的单核细胞在IFN-γ刺激时无法控制菌株.
- 缺乏IRF1的纤维细胞对包括SARS-CoV-2在内的9种病毒具有接近正常的抗病毒免疫力.
结论:
- 人类IRF1对于IFN-γ依赖的对菌根的巨免疫是必不可少的.
- 人类的IRF1在很大程度上是对IFN-α/β依赖的内在抗病毒免疫的冗余.
- 缺少IRF1主要影响对抗巨内病原体,而不是病毒.
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