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Aspergillus fumigatus regulates mite allergen-pulsed dendritic cells in the development of asthma.

机译:烟曲霉在哮喘的发生过程中调节螨过敏原刺激的树突状细胞。

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BACKGROUND: The role in allergic asthma development of the immune response against fungi with concomitant exposure to other common aeroallergens has yet to be determined. In particular, there is little understanding of how inhaled fungi affect the host response to mite allergens. OBJECTIVE: To characterize the in vitro and in vivo effects of concurrent exposure of Aspergillus fumigatus (Af) and Dermatophagoides farinae (Derf) on dendritic cells (DCs) in the development of allergic asthma. METHODS: Murine bone marrow-derived DCs were pulsed with Derf and/or live or heat-inactivated Af. Cytokine production and the expression of pathogen recognition receptors (PRRs) were determined in vitro. Subsequently, these DCs were inoculated into the airway of naive mice to assess the development of allergic airway inflammation in vivo. The effect of antibodies against PRRs was also evaluated. RESULTS: Live Af significantly enhanced IL-10 production and the expression of Toll-like receptor (TLR) 2 and Dectin-1 in Derf-pulsed DCs. Live Af infection significantly attenuated Derf-pulsed DC-induced allergic airway inflammation in vivo. Antibodies against either TLR2 or Dectin-1 significantly reversed the inhibitory effects of live Af in the development of Derf-pulsed DC-induced allergic airway inflammation. CONCLUSION: Concurrent exposure of DCs to fungal antigens has profound influences on the subsequent mite allergen-induced allergic airway inflammation. Live Af could regulate the functions of airway DCs in the development of mite allergen-induced allergic airway inflammation via regulation of their PRRs. Our results suggest that concurrent exposure to pathogens such as fungi and mite allergens has profound influences on the subsequent allergen-induced allergic airway inflammation. Furthermore, modulating PRR signalling could provide a therapeutic regimen for the development of asthma.
机译:背景:在过敏性哮喘的发展中,针对真菌的免疫反应以及同时接触其他常见的空气过敏原的作用尚未确定。特别是,对吸入真菌如何影响宿主对螨过敏原的反应了解甚少。目的:研究在过敏性哮喘发展过程中,烟熏曲霉(Af)和烟曲霉(Dermatophagoides farinae)(Derf)同时暴露于树突状细胞(DC)的体外和体内效应。方法:用Derf和/或活或热灭活的Af对小鼠骨髓来源的DC进行脉冲处理。体外测定细胞因子的产生和病原体识别受体(PRRs)的表达。随后,将这些DC接种到幼稚小鼠的气道中以评估体内过敏性气道炎症的发展。还评估了针对PRR的抗体的作用。结果:活的Af显着增强了Derf脉冲DC中IL-10的产生以及Toll样受体(TLR)2和Dectin-1的表达。活的Af感染可显着减轻Derf脉冲DC诱导的体内过敏性气道炎症。针对TLR2或Dectin-1的抗体可显着逆转活Af在Derf脉冲DC诱导的过敏性气道炎症发展过程中的抑制作用。结论:DCs同时暴露于真菌抗原对随后的螨过敏原诱发的过敏性气道炎症具有深远的影响。 Live Af可以通过调节其PRR来调节螨过敏原诱发的过敏性气道炎症发展中的气道DC功能。我们的结果表明,同时暴露于病原体(如真菌和螨过敏原)对随后的过敏原诱发的过敏性气道炎症具有深远的影响。此外,调节PRR信号传导可为哮喘的发展提供治疗方案。

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