Prevention of Influenza Virus-Induced Immunopathology by TGF-β Produced during Allergic Asthma.
Prevention of Influenza Virus-Induced Immunopathology by TGF-β Produced during Allergic Asthma.
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DOI：
10.1371/journal.ppat.1005180
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发表时间：
2015-09
期刊：
影响因子：
6.7
通讯作者：
Metzger DW
中科院分区：
文献类型：
--
作者：
Furuya Y;Furuya AK;Roberts S;Sanfilippo AM;Salmon SL;Metzger DW
哮喘被认为是流感感染的危险因素，但几乎没有实验证据直接证明哮喘对流感感染的易感性。使用小鼠模型，我们现在报告说，哮喘小鼠实际上对致命流感病毒的挑战具有明显更强的抵抗力。值得注意的是，观察到的耐药性增加并不是由于病毒清除的增强，而是由于肺部炎症的减少。哮喘小鼠表现出细胞因子风暴显著减少，以及呼吸道总蛋白水平和细胞毒性降低，这是组织损伤减少的指标。此外，哮喘小鼠的转化生长因子-β-1水平显著升高，在没有转化生长因子-β受体II的情况下，哮喘小鼠抵抗力的增强被抑制。我们认为，急性哮喘后转化生长因子-β表达的一过性增加可以诱导对流感诱导的免疫病理的保护作用。流感和哮喘是人类的两种主要肺部疾病。虽然大多数研究都集中在流感病毒感染加剧哮喘症状上，但对哮喘对流感病毒感染易感性的影响的研究要少得多。使用一种新的哮喘和流感感染的小鼠模型，我们发现与非哮喘小鼠相比，哮喘小鼠对2009年流感大流行毒株(CA04)的初始挑战具有高度的抵抗力。哮喘小鼠抵抗力的增强不是由于T或B细胞免疫增强，而是由于哮喘引发了强大的抗炎性转化生长因子-β反应。这项研究首次为2009年流感大流行期间哮喘介导的保护提供了机制解释。
Asthma is believed to be a risk factor for influenza infection, however little experimental evidence exists to directly demonstrate the impact of asthma on susceptibility to influenza infection. Using a mouse model, we now report that asthmatic mice are actually significantly more resistant to a lethal influenza virus challenge. Notably, the observed increased resistance was not attributable to enhanced viral clearance, but instead, was due to reduced lung inflammation. Asthmatic mice exhibited a significantly reduced cytokine storm, as well as reduced total protein levels and cytotoxicity in the airways, indicators of decreased tissue injury. Further, asthmatic mice had significantly increased levels of TGF-β1 and the heightened resistance of asthmatic mice was abrogated in the absence of TGF-β receptor II. We conclude that a transient increase in TGF-β expression following acute asthma can induce protection against influenza-induced immunopathology. Influenza and asthma represent the two major lung diseases in humans. While most studies have focused on exacerbation of asthma symptoms by influenza virus infection, the effects of asthma on susceptibility to influenza virus infections has been far less studied. Using a novel mouse model of asthma and influenza infection, we show that asthmatic mice are highly resistant to primary challenge with the 2009 influenza pandemic strain (CA04) compared to non-asthmatic mice. The increased resistance of asthmatic mice is not due to the enhanced T or B cell immunity but rather, to a strong anti-inflammatory TGF-beta response triggered by asthma. This study is the first to provide a mechanistic explanation for asthma-mediated protection during the 2009 influenza pandemic.