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Native and IgE-primed rat peritoneal mast cells exert pro-inflammatory activity and migrate in response to yeast zymosan upon Dectin-1 engagement
Immunologic Research ( IF 3.3 ) Pub Date : 2021-03-11 , DOI: 10.1007/s12026-021-09183-7
Paulina Żelechowska 1 , Ewa Brzezińska-Błaszczyk 1 , Sylwia Różalska 2 , Justyna Agier 1 , Elżbieta Kozłowska 1
Affiliation  

Mast cells (MCs) play an essential role in host defense, primarily because of their location, their ability to pathogen destruction via several mechanisms, and the pattern recognition receptors they express. Even though most data is available regarding MC activation by various bacteria- or virus-derived molecules, those cells’ activity in response to constituents associated with fungi is not recognized enough. Our research aimed to address whether Saccharomyces cerevisiae-derived zymosan, i.e., β-(1,3)-glucan containing mannan particles, impacts MC activity aspects. Overall, the obtained results indicate that zymosan has the potential to elicit a pro-inflammatory response of rat peritoneal MCs. For the first time ever, we provided evidence that zymosan induces fully mature MC migration, even in the absence of extracellular matrix (ECM) proteins. Moreover, the zymosan-induced migratory response of MCs is almost entirely a result of directional migration, i.e., chemotaxis. We found that zymosan stimulates MCs to degranulate and generate lipid mediators (cysLTs), cytokines (IFN-α, IFN-β, IFN-γ, GM-CSF, TNF), and chemokine (CCL2). Zymosan also upregulated mRNA transcripts for several cytokines/chemokines with pro-inflammatory/immunoregulatory activity. Moreover, we documented that zymosan activates MCs to produce reactive oxygen species (ROS). Lastly, we established that the zymosan-induced MC response is mediated through activation of the Dectin-1 receptor. In general, our results strongly support the notion that MCs contribute to innate antifungal immunity and bring us closer to elucidate their role in host-pathogenic fungi interactions. Besides, provided findings on IgE-sensitized MCs appear to indicate that exposure to fungal zymosan could affect the severity of IgE-dependent disorders, including allergic ones.



中文翻译:


天然和 IgE 引发的大鼠腹膜肥大细胞发挥促炎活性,并在 Dectin-1 参与后响应酵母聚糖而迁移



肥大细胞 (MC) 在宿主防御中发挥着重要作用,主要是因为它们的位置、它们通过多种机制破坏病原体的能力以及它们表达的模式识别受体。尽管大多数数据都涉及各种细菌或病毒衍生分子对 MC 的激活,但这些细胞对真菌相关成分的反应活性尚未得到充分认识。我们的研究旨在解决酿酒酵母衍生的酵母聚糖(即含有甘露聚糖颗粒的 β-(1,3)-葡聚糖)是否影响 MC 活性方面​​。总体而言,获得的结果表明酵母聚糖有可能引发大鼠腹膜 MC 的促炎反应。我们首次提供证据表明,即使在没有细胞外基质 (ECM) 蛋白的情况下,酵母聚糖也能诱导完全成熟的 MC 迁移。此外,酵母聚糖诱导的MCs迁移反应几乎完全是定向迁移的结果,即趋化性。我们发现酵母聚糖刺激 MC 脱颗粒并产生脂质介质 (cysLT)、细胞因子(IFN-α、IFN-β、IFN-γ、GM-CSF、TNF)和趋化因子 (CCL2)。酵母聚糖还上调了几种具有促炎/免疫调节活性的细胞因子/趋化因子的 mRNA 转录本。此外,我们记录了酵母聚糖激活 MC 产生活性氧 (ROS)。最后,我们确定酵母聚糖诱导的 MC 反应是通过 Dectin-1 受体的激活介导的。总的来说,我们的结果强烈支持了 MC 有助于先天抗真菌免疫的观点,并使我们更接近于阐明它们在宿主与病原真菌相互作用中的作用。 此外,对 IgE 致敏 MC 的研究结果似乎表明,接触真菌酵母聚糖可能会影响 IgE 依赖性疾病(包括过敏性疾病)的严重程度。

更新日期:2021-03-11
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