Mannan activates tissue native and IgE‐sensitized mast cells to proinflammatory response and chemotaxis in TLR4‐dependent manner
Mannan activates tissue native and IgE‐sensitized mast cells to proinflammatory response and chemotaxis in TLR4‐dependent manner
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DOI：
10.1002/jlb.4a0720-452r
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发表时间：
2020-10
影响因子：
5.5
通讯作者：
P. Żelechowska;E. Brzezińska‐Błaszczyk;S. Różalska;J. Agier;E. Kozłowska
中科院分区：
文献类型：
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作者：
P. Żelechowska;E. Brzezińska‐Błaszczyk;S. Różalska;J. Agier;E. Kozłowska
肥大细胞在感染门静脉处数量众多，参与宿主对微生物的防御，发挥几种重要的病原体破坏机制，并表达模式识别受体。越来越多的证据表明，这些细胞参与控制和清除细菌、病毒或寄生虫感染，但对它们在防御真菌方面的作用知之甚少。甘露聚糖是真菌细胞壁的最外层和主要结构成分，该研究旨在确定甘露聚糖是否可以直接刺激组织肥大细胞产生抗真菌反应。我们的研究结果表明，甘露聚糖激活从大鼠腹腔分离的肥大细胞，启动促炎反应。我们发现甘露聚糖刺激肥大细胞释放组胺并产生半胱氨酸白三烯、细胞因子（IFN‐γ、GM‐CSF、TNF）和趋化因子（CCL2、CCL3）。它还增加了各种细胞因子/趋化因子的mRNA表达。我们还记录了甘露聚糖强烈激活肥大细胞产生活性氧，并作为这些细胞的有效化学引诱剂。此外，我们确定甘露聚糖诱导肥大细胞的活性是通过TLR4介导的，并参与脾脏酪氨酸激酶分子。综上所述，我们的结果清楚地支持肥大细胞作为前哨细胞的观点，并在真菌感染期间至关重要地决定了免疫反应的过程。此外，关于IgE包被肥大细胞的现有数据表明，暴露于真菌甘露聚糖可能会影响IgE依赖性疾病的严重程度，包括过敏性疾病。
Mast cells take part in host defense against microorganisms as they are numerous at the portal of infection, exert several essential mechanisms of pathogen destruction, and they express pattern recognition receptors. Accumulating evidence indicates that these cells are involved in the control and clearance of bacterial, viral, or parasitic infections, but much less is known about their contribution in defense against fungi. The study was aimed to establish whether mannan, which comprises an outermost layer and major structural constituent of the fungal cell wall, may directly stimulate tissue mast cells to the antifungal response. Our findings indicate that mannan activates mast cells isolated from the rat peritoneal cavity to initiate the proinflammatory response. We found that mannan stimulates mast cells to release histamine and to generate cysteinyl leukotrienes, cytokines (IFN‐γ, GM‐CSF, TNF), and chemokines (CCL2, CCL3). It also increased the mRNA expression of various cytokines/chemokines. We also documented that mannan strongly activates mast cells to generate reactive oxygen species and serves as a potent chemoattractant for these cells. Furthermore, we established that mannan‐induced activity of mast cells is mediated via TLR4 with the involvement of the spleen tyrosine kinase molecule. Taking together, our results clearly support the idea that mast cells act as sentinel cells and crucially determine the course of the immune response during fungal infection. Additionally, presented data on IgE‐coated mast cells suggest that exposure to fungal mannan could influence the severity of IgE‐dependent diseases, including allergic ones.