title: Cell type-specific differences in β-glucan recognition and signalling in porcine innate immune cells.
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.
authors.affiliation: Laboratory of Immunology, Faculty of Veterinary Medicine, Ghent University, Salisburylaan 133, Merelbeke 9820, Belgium. Electronic address: ksbaert.baert@ugent.be.
authors.forename: Kim
authors.initials: K
authors.lastname: Baert
authors.affiliation: Laboratory of Immunology, Faculty of Veterinary Medicine, Ghent University, Salisburylaan 133, Merelbeke 9820, Belgium.
authors.forename: Eva
authors.initials: E
authors.lastname: Sonck
authors.affiliation: Laboratory of Immunology, Faculty of Veterinary Medicine, Ghent University, Salisburylaan 133, Merelbeke 9820, Belgium; Vaccine Design, Department of Biosystems, Faculty of Bioscience Engineering, K.U. Leuven, Kasteelpark Arenberg 30 bus 2456, Heverlee B-3001, Belgium.
authors.forename: Bruno M
authors.initials: BM
authors.lastname: Goddeeris
authors.affiliation: Laboratory of Immunology, Faculty of Veterinary Medicine, Ghent University, Salisburylaan 133, Merelbeke 9820, Belgium.
authors.forename: Bert
authors.initials: B
authors.lastname: Devriendt
authors.affiliation: Laboratory of Immunology, Faculty of Veterinary Medicine, Ghent University, Salisburylaan 133, Merelbeke 9820, Belgium.
authors.forename: Eric
authors.initials: E
authors.lastname: Cox
mesh_terms: D000818:Animals; D016207:Cytokines / Q000096:biosynthesis; D051416:Focal Adhesion Protein-Tyrosine Kinases / Q000276:immunology; D007113:Immunity, Innate / Q000276:immunology; D056747:Immunomodulation / Q000276:immunology; D047908:Intracellular Signaling Peptides and Proteins / Q000276:immunology; D037181:Lectins, C-Type / Q000235:genetics / Q000276:immunology*; D016177:Macrophage-1 Antigen / Q000235:genetics / Q000276:immunology*; D008264:Macrophages / Q000276:immunology; D009504:Neutrophils / Q000276:immunology; D010587:Phagocytosis / Q000235:genetics / Q000276:immunology*; D011505:Protein-Tyrosine Kinases / Q000276:immunology; D034622:RNA Interference; D034741:RNA, Small Interfering; D017382:Reactive Oxygen Species / Q000276:immunology; D016897:Respiratory Burst / Q000276:immunology; D015398:Signal Transduction / Q000276:immunology; D013552:Swine / Q000276:immunology*; D000072377:Syk Kinase; D047071:beta-Glucans / Q000276:immunology*; D000099181:Dectin-1
chemical_list: D016207:Cytokines; D051416:Focal Adhesion Protein-Tyrosine Kinases; D047908:Intracellular Signaling Peptides and Proteins; D037181:Lectins, C-Type; D016177:Macrophage-1 Antigen; D011505:Protein-Tyrosine Kinases; D034741:RNA, Small Interfering; D017382:Reactive Oxygen Species; D000072377:Syk Kinase; D047071:beta-Glucans; D000099181:Dectin-1; C000606897:Syk protein, mouse
keywords: CR3; Dectin-1; Innate immune cells; Pig; Signalling transduction; β-glucans