先天免疫失调与感染性和自身免疫性疾病密切相关。为了更好地了解这些疾病的发病机制和改善管理,实施系统先天免疫的便捷监测至关重要。建立在我们之前关于宿主对外周血感染的转录反应的工作基础上,我们提出了一个二维基因模型,用于同时评估系统先天免疫的两个主要组成部分,包括VirSig作为宿主对病毒感染的应答的标志和BacSig作为宿主对细菌感染的应答的标志。通过该2D基因模型在先天免疫中的失调的启示用各种各样的转录组数据集证明。在急性感染中,在病毒和细菌感染中观察到VirSig和BacSig激活的独特模式。相比之下,在绝大多数健康成年人中,这两个特征都被限制在确定的范围内,不管年龄。此外,BacSig在怀孕期间显示出显着升高,在发育过程中呈上升趋势。在结核病(TB)中,BacSig和VirSig的升高在大部分活动性TB患者中观察到,异常的BacSig也与更长的疗程有关。在囊性纤维化(CF)中,在一部分患者中观察到异常的BacSig,药物治疗后,未观察到BacSig异常的总体变化。在系统性硬化症相关的间质性肺病(SSc-ILD)中,在一些患者中观察到VirSig和BacSig显著升高,药物治疗导致BacSig进一步偏离对照水平。在系统性红斑狼疮(SLE)中,抗Ro自身抗体阳性与SLE患者VirSig显著升高相关,在妊娠期间的SLE患者中也观察到VirSig/BacSig激活的累加效应。总的来说,这些数据表明,2D基因模型可用于评估健康和疾病中的系统性先天免疫,具有潜在的临床应用,包括患者分层,抗生素处方,了解发病机理,和纵向监测治疗反应。
Dysregulation of innate immunity is deeply involved in infectious and autoimmune diseases. For a better understanding of pathogenesis and improved management of these diseases, it is of vital importance to implement convenient monitoring of systemic innate immunity. Built upon our previous works on the host transcriptional response to infection in peripheral blood, we proposed a 2D gene model for the simultaneous assessment of two major components of systemic innate immunity, including VirSig as the signature of the host response to viral infection and BacSig as the signature of the host response to bacterial infection. The revelation of dysregulation in innate immunity by this 2D gene model was demonstrated with a wide variety of transcriptome datasets. In acute infection, distinctive patterns of VirSig and BacSig activation were observed in viral and bacterial infection. In comparison, both signatures were restricted to a defined range in the vast majority of healthy adults, regardless of age. In addition, BacSig showed significant elevation during pregnancy and an upward trend during development. In tuberculosis (TB), elevation of BacSig and VirSig was observed in a significant portion of active TB patients, and abnormal BacSig was also associated with a longer treatment course. In cystic fibrosis (CF), abnormal BacSig was observed in a subset of patients, and no overall change in BacSig abnormality was observed after the drug treatment. In systemic sclerosis-associated interstitial lung disease (SSc-ILD), significant elevation of VirSig and BacSig was observed in some patients, and treatment with a drug led to the further deviation of BacSig from the control level. In systemic lupus erythematosus (SLE), positivity for the anti-Ro autoantibody was associated with significant elevation of VirSig in SLE patients, and the additive effect of VirSig/BacSig activation was also observed in SLE patients during pregnancy. Overall, these data demonstrated that the 2D gene model can be used to assess systemic innate immunity in health and disease, with the potential clinical applications including patient stratification, prescription of antibiotics, understanding of pathogenesis, and longitudinal monitoring of treatment response.