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.

中文翻译：

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甘露聚糖以TLR4依赖性方式激活组织天然和IgE敏感的肥大细胞对促炎反应和趋化性

肥大细胞参与了宿主对微生物的防御，因为它们在感染的门口数量众多，发挥了几种破坏病原体的基本机制，并表达模式识别受体。越来越多的证据表明，这些细胞参与细菌，病毒或寄生虫感染的控制和清除，但人们对它们对真菌防御的贡献知之甚少。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，甘露聚糖由最外层和真菌细胞壁的主要结构组成。我们的发现表明甘露聚糖激活了从大鼠腹膜腔分离出的肥大细胞以启动促炎反应。我们发现甘露聚糖刺激肥大细胞释放组胺并生成半胱氨酰白三烯，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以产生活性氧，并充当这些细胞的强力化学吸引剂。此外，我们确定甘露聚糖诱导的肥大细胞活性是通过TLR4在脾酪氨酸激酶分子的参与下介导的。综上所述，我们的结果清楚地支持了肥大细胞充当前哨细胞，并在真菌感染过程中决定性地决定了免疫反应进程的观点。此外，