Laboratory of Immunology, Department of Virology, Parasitology and Immunology, Faculty of Veterinary Medicine, Ghent University, Merelbeke, Belgium.
Front Immunol. 2021 Feb 19;12:634402. doi: 10.3389/fimmu.2021.634402. eCollection 2021.
Beta-glucans are naturally occurring polysaccharides present in cell walls of fungi, yeast, bacteria, cereals, seaweed, and algae. These microbe-associated molecular patterns (MAMPs) possess immunomodulatory properties. In human, it has been suggested that NK cells can be activated by β-glucans. Here, we aimed to elucidate whether β-glucans modulate porcine NK cell responses and if so, how these effects are mediated. We investigated the effect of two β-glucans, Macrogard and Curdlan, which differ in solubility and structure. Direct addition of β-glucans to purified porcine NK cells did not affect cytotoxicity of these cells against K562 target cells. However, when using PBMC instead of purified NK cells, β-glucan addition significantly increased NK cell-mediated cytotoxicity. This effect depended on factors secreted by CD14+ monocytes upon β-glucan priming. Further analysis showed that monocytes secrete TNF-α, IL-6, and IL-10 upon β-glucan addition. Of these, IL-10 turned out to play a critical role in β-glucan-triggered NK cell cytotoxicity, since depletion of IL-10 completely abrogated the β-glucan-induced increase in cytotoxicity. Furthermore, addition of recombinant IL-10 to purified NK cells was sufficient to enhance cytotoxicity. In conclusion, we show that β-glucans trigger IL-10 secretion by porcine monocytes, which in turn leads to increased NK cell cytotoxicity, and thereby identify IL-10 as a potent stimulus of porcine NK cell cytotoxicity.
β-葡聚糖是存在于真菌、酵母、细菌、谷物、海藻和藻类细胞壁中的天然多聚糖。这些微生物相关的分子模式（MAMPs）具有免疫调节特性。在人类中，已经表明 NK 细胞可以被β-葡聚糖激活。在这里，我们旨在阐明β-葡聚糖是否调节猪 NK 细胞的反应，如果是，这些影响是如何介导的。我们研究了两种β-葡聚糖，即 Macrogard 和 Curdlan，它们在溶解度和结构上有所不同。β-葡聚糖直接添加到纯化的猪 NK 细胞中不会影响这些细胞对 K562 靶细胞的细胞毒性。然而，当使用 PBMC 而不是纯化的 NK 细胞时，β-葡聚糖的添加显著增加了 NK 细胞介导的细胞毒性。这种效应取决于 CD14+单核细胞在β-葡聚糖引发时分泌的因子。进一步的分析表明，单核细胞在添加β-葡聚糖后会分泌 TNF-α、IL-6 和 IL-10。在这些细胞因子中，IL-10 被证明在β-葡聚糖触发的 NK 细胞细胞毒性中起着关键作用，因为 IL-10 的耗竭完全消除了β-葡聚糖诱导的细胞毒性增加。此外，向纯化的 NK 细胞中添加重组 IL-10 足以增强细胞毒性。总之，我们表明β-葡聚糖触发猪单核细胞分泌 IL-10，进而导致 NK 细胞细胞毒性增加，从而确定 IL-10 是猪 NK 细胞细胞毒性的有效刺激物。
