Cell type-specific differences in β-glucan recognition and signalling in porcine innate immune cells
Cell type-specific differences in β-glucan recognition and signalling in porcine innate immune cells
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DOI：
10.1016/j.dci.2014.10.005
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发表时间：
2015-01-01
影响因子：
2.9
通讯作者：
Cox, Eric
中科院分区：
文献类型：
--
作者：
Baert, Kim;Sonck, Eva;Cox, Eric
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（CR 3）在免疫细胞对β-葡聚糖的反应中的作用仍然没有得到解决。Dectin-1被认为是小鼠中主要的β-葡聚糖受体，而最近对人类的研究表明，CR 3在β-葡聚糖介导的反应中更重要。这促使我们阐明哪种受体有助于猪先天免疫细胞对颗粒β-葡聚糖的反应，因为后者可能是人类的更好模型。我们的研究结果表明，CR 3在β-葡聚糖识别中发挥重要作用，因为阻断这种受体强烈降低了β-葡聚糖的吞噬作用和β-葡聚糖诱导的猪嗜中性粒细胞的ROS产生。相反，dectin-1似乎在嗜中性粒细胞的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CR 3都参与了猪巨噬细胞中β-葡聚糖介导的反应。此外，通过黏着斑激酶（FAK）的CR 3信号传导对于嗜中性粒细胞和巨噬细胞中β-葡聚糖介导的ROS产生和细胞因子产生是必不可少的，而Syk依赖性途径仅部分参与这些反应。我们可以得出结论，CR 3在猪中性粒细胞中β-葡聚糖信号传导中起着重要作用，而巨噬细胞使用更多样化的受体阵列来检测β-葡聚糖并对其做出反应。尽管如此，FAK作为一个主开关，调节β-葡聚糖介导的反应，在嗜中性粒细胞以及巨噬细胞。(C)2014爱思唯尔有限公司版权所有。
beta-glucans exert receptor-mediated immunomodulating activities, including oxidative burst activity and cytokine secretion. The role of the beta-glucan receptors dectin-1 and complement receptor 3 (CR3) in the response of immune cells towards beta-glucans is still unresolved. Dectin-1 is considered as the main beta-glucan receptor in mice, while recent studies in man show that CR3 is more important in beta-glucan-mediated responses. This incited us to elucidate which receptor contributes to the response of innate immune cells towards particulate beta-glucans in pigs as the latter might serve as a better model for man. Our results show an important role of CR3 in beta-glucan recognition, as blocking this receptor strongly reduced the phagocytosis of beta-glucans and the beta-glucan-induced ROS production by porcine neutrophils. Conversely, dectin-1 does not seem to play a major role in beta-glucan recognition in neutrophils. However, recognition of beta-glucans appeared cell type-specific as both dectin-1 and CR3 are involved in the beta-glucanmediated responses in pig macrophages. Moreover, CR3 signalling through focal adhesion kinase (FAK) was indispensable for beta-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 beta-glucan signalling in porcine neutrophils, while macrophages use a more diverse receptor array to detect and respond towards beta-glucans. Nonetheless, FAK acts as a master switch that regulates beta-glucan-mediated responses in neutrohils as well as macrophages. (C) 2014 Elsevier Ltd. All rights reserved.