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首页> 外文期刊>Allergy >Th2 cytokines impair innate immune responses to rhinovirus in respiratory epithelial cells
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Th2 cytokines impair innate immune responses to rhinovirus in respiratory epithelial cells

机译：Th2细胞因子削弱呼吸道上皮细胞对鼻病毒的先天免疫应答

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Background: Asthma and other Th2 inflammatory conditions have been associated with increased susceptibility to viral infections. The mechanisms by which Th2 cytokines can influence immune responses to infections are largely unknown. Methods: We measured the effects of Th2 cytokines (IL-4 and IL-13) on bronchial epithelial cell innate immune antiviral responses by assessing interferon (IFN-P and IFN-X1) induction following rhinovirus (RV)-16 infection. We also investigated the modulatory effects of Th2 cytokines on Toll-like receptor 3 (TLR3), interferon-responsive factor 3 (IRF3) and nuclear factor (NF)-kB, that is key molecules and transcription factors involved in the rhinovirus-induced interferon production and inflammatory cascade. Pharmacological and redox modulation of these pathways was also assessed. Results: Th2 cytokines impaired RV-16-induced interferon production, increased rhinovirus replication and impaired TLR3 expression in bronchial epithelial cells. These results were replicated in vivo: we found increased IL-4 mRNA levels in nasal epithelial cells from nasal brushing of atopic rhinitis patients and a parallel reduction in TLR3 expression and increased RV-16 replication compared to nonatopic subjects. Mechanistically, Th2 cytokines impaired RV-16-induced activation of IRF3, but had no effects on RV-16-induced NF-kB activation in bronchial epithelial cell cultures. N-acetylcysteine and phosphoinositide 3-kinase (PI3K) inhibitor restored the inhibitory effects of Th2 cytokines over RV-16-induced activation of IRF3. Conclusions: IL-4 and IL-13, through inhibition of TLR3 expression and signalling (IRF3), impair immune response to RV-16 infection. These data suggest that Th2 conditions increase susceptibility to infections and identify pharmacological approaches with potential to restore impaired immune response in these conditions.
机译：背景：哮喘和其他Th2炎症性疾病与病毒感染的易感性增加有关。 Th2细胞因子影响感染免疫反应的机制尚不清楚。方法：我们通过评估鼻病毒（RV）-16感染后的干扰素（IFN-P和IFN-X1）诱导，测量了Th2细胞因子（IL-4和IL-13）对支气管上皮细胞先天免疫抗病毒反应的影响。我们还研究了Th2细胞因子对Toll样受体3（TLR3），干扰素反应因子3（IRF3）和核因子（NF）-kB的调节作用，这是鼻病毒诱导的干扰素中涉及的关键分子和转录因子。产生和炎症级联。还评估了这些途径的药理学和氧化还原调节。结果：Th2细胞因子损害了RV-16诱导的干扰素产生，鼻病毒复制增加和支气管上皮细胞中TLR3表达受损。这些结果在体内得到了复制：与非特应性受试者相比，我们发现特应性鼻炎患者经鼻刷洗后鼻腔上皮细胞中IL-4 mRNA水平增加，TLR3表达平行降低，RV-16复制增加。从机制上讲，Th2细胞因子损害了RV-16诱导的IRF3的激活，但对RV-16诱导的支气管上皮细胞培养物中的NF-kB激活没有影响。 N-乙酰半胱氨酸和磷酸肌醇3激酶（PI3K）抑制剂恢复了Th2细胞因子对RV-16诱导的IRF3激活的抑制作用。结论：IL-4和IL-13通过抑制TLR3表达和信号传导（IRF3）削弱了对RV-16感染的免疫反应。这些数据表明，Th2疾病增加了对感染的敏感性，并确定了在这些疾病中具有恢复受损免疫反应潜能的药理学方法。

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