哮喘急性加重模型屋尘螨通过TLR3破坏抗病毒作用

2018/01/19

   摘要
   背景:破坏抗病毒干扰素的表达参与发生在因鼻病毒引起的哮喘急性加重。国民是病毒诱导哮喘发作已知的危险因素,但过敏原如何影响干扰素的作用机制并不明确。
   目的:我们假设屋尘螨(HDM)破坏病毒刺激物诱导抗病毒信号通路。
   方法:在体外人气道上皮细胞(HBECs)上诱导哮喘急性加重,在小鼠应用HDM逐步刺激和病毒感染类似物Poly(I:C)进行诱导。研究观察鼻病毒模式识别受体(PRRs)信号通路和干扰素反应受损的潜在机制。
   结果:HBECs和小鼠在Poly(I:C)刺激前接触HDM,与单独接受Poly(I:C)刺激相比,前者抗病毒反应下降,包括IFN-β, IFN-λ, TLR3, RIG-I, MDA5, IRF-3 和IRF-7表达下降。在体内和体外,HDM热灭活可以部分恢复TLR3诱导干扰素功能。HBEC数据进一步提示HDM通过受体糖基化水平调节直接影响TLR3信号通路。
   结论:诸如HDM等过敏原直接作用于PRRs可以代表抗病毒气道反应缺陷的潜在机制所在。相对应的,针对上述过程的抑制性治疗可以增强抗病毒反应并改善哮喘患者急性加重情况。

 

(上海交通大学医学院附属瑞金医院呼吸与危重症医学科 周剑平 万欢英 摘译)

(Allergy. 2018 Jan 10. doi: 10.1111/all.13378. [Epub ahead of print])

 

House dust mite impairs antiviral response in asthma exacerbation models through its effects on TLR3.

 

Allergy. 2018 Jan 10. doi: 10.1111/all.13378. [Epub ahead of print]

Akbarshahi H et al.
 
Abstract
BACKGROUND:Impaired antiviral interferon expression may be involved in asthma exacerbations commonly caused by rhinovirus infections. Allergy is a known risk factor for viral-induced asthma exacerbation, but little is known whether allergens may affect interferon responses.
OBJECTIVE:Our hypothesis is that house dust mite (HDM) impairs viral stimulus-induced antiviral signalling.
METHODS:Experimental asthma exacerbations were produced in vitro in human bronchial epithelial cells (HBECs) and in mice by using sequential challenges with HDM and a viral infection mimic, Poly(I:C). We examined rhinovirus pattern recognition receptors (PRRs) signalling pathways and potential mechanisms of impaired interferon response.
RESULTS:HBECs and mice exposed to HDM prior to Poly(I:C) exhibited a reduced antiviral response compared to Poly(I:C) alone, including reduced IFN-β, IFN-lambda, TLR3, RIG-I, MDA5, IRF-3 and IRF-7. Heat-inactivation of HDM partially restored the TLR3-induced interferon response in vitro and in vivo. Our HBEC-data further showed that HDM directly affects TLR3 signalling by targeting the receptor glycosylation level.
CONCLUSIONS:Direct effects of allergens such as HDM on PRRs can present as potential mechanism for defective antiviral airway responses. Accordingly, therapeutic measures targeting inhibitory effects of allergens on antiviral PRRs may find use as a strategy to boost antiviral response and ameliorate exacerbations in asthmatic patients.
 


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