Baert Kim, Sonck Eva, Goddeeris Bruno M, Devriendt Bert, Cox Eric
Laboratory of Immunology, Faculty of Veterinary Medicine, Ghent University, Salisburylaan 133, Merelbeke 9820, Belgium.
Laboratory of Immunology, Faculty of Veterinary Medicine, Ghent University, Salisburylaan 133, Merelbeke 9820, Belgium.
Dev Comp Immunol. 2015 Jan;48(1):192-203. doi: 10.1016/j.dci.2014.10.005. Epub 2014 Oct 22.
β-glucans exert receptor-mediated immunomodulating activities, including oxidative burst activity and cytokine secretion. The role of the β-glucan receptors dectin-1 and complement receptor 3 (CR3) in the response of immune cells towards β-glucans is still unresolved. Dectin-1 is considered as the main β-glucan receptor in mice, while recent studies in man show that CR3 is more important in β-glucan-mediated responses. This incited us to elucidate which receptor contributes to the response of innate immune cells towards particulate β-glucans in pigs as the latter might serve as a better model for man. Our results show an important role of CR3 in β-glucan recognition, as blocking this receptor strongly reduced the phagocytosis of β-glucans and the β-glucan-induced ROS production by porcine neutrophils. Conversely, dectin-1 does not seem to play a major role in β-glucan recognition in neutrophils. However, recognition of β-glucans appeared cell type-specific as both dectin-1 and CR3 are involved in the β-glucan-mediated responses in pig macrophages. Moreover, CR3 signalling through focal adhesion kinase (FAK) was indispensable for β-glucan-mediated ROS production and cytokine production in neutrophils and macrophages, while the Syk-dependent pathway was only partly involved in these responses. We may conclude that CR3 plays a cardinal role in β-glucan signalling in porcine neutrophils, while macrophages use a more diverse receptor array to detect and respond towards β-glucans. Nonetheless, FAK acts as a master switch that regulates β-glucan-mediated responses in neutrophils as well as macrophages.
β-葡聚糖发挥受体介导的免疫调节活性，包括氧化爆发活性和细胞因子分泌。β-葡聚糖受体dectin-1和补体受体3（CR3）在免疫细胞对β-葡聚糖反应中的作用仍未明确。Dectin-1被认为是小鼠中的主要β-葡聚糖受体，而最近在人类中的研究表明CR3在β-葡聚糖介导的反应中更重要。这促使我们去阐明哪种受体有助于猪先天免疫细胞对颗粒状β-葡聚糖的反应，因为猪可能是更适合人类的模型。我们的结果表明CR3在β-葡聚糖识别中起重要作用，因为阻断该受体可强烈降低猪中性粒细胞对β-葡聚糖的吞噬作用以及β-葡聚糖诱导的活性氧生成。相反，dectin-1似乎在中性粒细胞的β-葡聚糖识别中不起主要作用。然而，β-葡聚糖的识别似乎具有细胞类型特异性，因为dectin-1和CR3都参与猪巨噬细胞中β-葡聚糖介导的反应。此外，通过粘着斑激酶（FAK）的CR3信号传导对于中性粒细胞和巨噬细胞中β-葡聚糖介导的活性氧生成和细胞因子生成是必不可少的，而Syk依赖性途径仅部分参与这些反应。我们可以得出结论，CR3在猪中性粒细胞的β-葡聚糖信号传导中起主要作用，而巨噬细胞使用更多样化的受体阵列来检测和响应β-葡聚糖。尽管如此，FAK作为一个主开关，调节中性粒细胞和巨噬细胞中β-葡聚糖介导的反应。
