Author:

Keywords:

beta-glucans, CR3, Dectin-1, Innate immune cells, Signalling transduction, Pig, Science & Technology, Life Sciences & Biomedicine, Fisheries, Immunology, Veterinary Sciences, Zoology, FOCAL ADHESION KINASE, BINDING LECTIN SITE, SYK TYROSINE KINASE, IMMUNOMODULATORY ACTIVITIES, SCAVENGER RECEPTORS, DECTIN-1, COMPLEMENT, NEUTROPHIL, RESPONSES, IDENTIFICATION, β-glucans, Animals, Cytokines, Focal Adhesion Protein-Tyrosine Kinases, Immunity, Innate, Immunomodulation, Intracellular Signaling Peptides and Proteins, Lectins, C-Type, Macrophage-1 Antigen, Macrophages, Neutrophils, Phagocytosis, Protein-Tyrosine Kinases, RNA Interference, RNA, Small Interfering, Reactive Oxygen Species, Respiratory Burst, Signal Transduction, Swine, Syk Kinase, beta-Glucans, 1107 Immunology, 3204 Immunology

Abstract:

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.