期刊
DEVELOPMENTAL AND COMPARATIVE IMMUNOLOGY
卷 48, 期 1, 页码 192-203出版社
ELSEVIER SCI LTD
DOI: 10.1016/j.dci.2014.10.005
关键词
beta-glucans; CR3; Dectin-1; Innate immune cells; Signalling transduction; Pig
资金
- Agency for Innovation by Science and Technology (IWT) [111424]
- Ghent University (Belgium)
- Hercules Foundation [AUGE035]
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.
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