title: Dectin-1 pathway activates robust autophagy-dependent unconventional protein secretion in human macrophages.
abstract: Dectin-1 is a membrane-bound pattern recognition receptor for β-glucans, which are the main constituents of fungal cell walls. Detection of β-glucans by dectin-1 triggers an effective innate immune response. In this study, we have used a systems biology approach to provide the first comprehensive characterization of the secretome and associated intracellular signaling pathways involved in activation of dectin-1/Syk in human macrophages. Transcriptome and secretome analysis revealed that the dectin-1 pathway induced significant gene expression changes and robust protein secretion in macrophages. The enhanced protein secretion correlated only partly with increased gene expression. Bioinformatics combined with functional studies revealed that the dectin-1/Syk pathway activates both conventional and unconventional, vesicle-mediated, protein secretion. The unconventional protein secretion triggered by the dectin-1 pathway is dependent on inflammasome activity and an active autophagic process. In conclusion, our results reveal that unconventional protein secretion has an important role in the innate immune response against fungal infections.
authors.affiliation: Institute of Biotechnology, University of Helsinki, 00014 Helsinki, Finland;
authors.forename: Tiina
authors.initials: T
authors.lastname: Öhman
authors.affiliation: Finnish Institute of Occupational Health, 00250 Helsinki, Finland;
authors.forename: Laura
authors.initials: L
authors.lastname: Teirilä
authors.affiliation: Computational Systems Biology Laboratory, Institute of Biomedicine, Genome-Scale Biology Research Program, Faculty of Medicine, University of Helsinki, 00014 Helsinki, Finland;
authors.forename: Anna-Maria
authors.initials: AM
authors.lastname: Lahesmaa-Korpinen
authors.affiliation: Institute of Biotechnology, University of Helsinki, 00014 Helsinki, Finland;
authors.forename: Wojciech
authors.initials: W
authors.lastname: Cypryk
authors.affiliation: Finnish Institute of Occupational Health, 00250 Helsinki, Finland;
authors.forename: Ville
authors.initials: V
authors.lastname: Veckman
authors.affiliation: Department of Molecular Immunology, Medical Mycology Research Center, Chiba University, Chiba 260-8673, Japan; and Presto, Japan Science and Technology Agency, Saitama 332-0012, Japan.
authors.forename: Shinobu
authors.initials: S
authors.lastname: Saijo
authors.affiliation: Finnish Institute of Occupational Health, 00250 Helsinki, Finland;
authors.forename: Henrik
authors.initials: H
authors.lastname: Wolff
authors.affiliation: Computational Systems Biology Laboratory, Institute of Biomedicine, Genome-Scale Biology Research Program, Faculty of Medicine, University of Helsinki, 00014 Helsinki, Finland;
authors.forename: Sampsa
authors.initials: S
authors.lastname: Hautaniemi
authors.affiliation: Institute of Biotechnology, University of Helsinki, 00014 Helsinki, Finland;
authors.forename: Tuula A
authors.initials: TA
authors.lastname: Nyman
authors.affiliation: Finnish Institute of Occupational Health, 00250 Helsinki, Finland; sampsa.matikainen@ttl.fi.
authors.forename: Sampsa
authors.initials: S
authors.lastname: Matikainen
mesh_terms: D001343:Autophagy / Q000276:immunology*; D005260:Female; D005786:Gene Expression Regulation / Q000276:immunology*; D006801:Humans; D007113:Immunity, Innate; D058847:Inflammasomes / Q000276:immunology* / Q000378:metabolism; D047908:Intracellular Signaling Peptides and Proteins / Q000276:immunology / Q000378:metabolism; D037181:Lectins, C-Type / Q000276:immunology*; D008264:Macrophages / Q000276:immunology* / Q000378:metabolism; D008297:Male; D009181:Mycoses / Q000276:immunology / Q000378:metabolism; D011505:Protein-Tyrosine Kinases / Q000276:immunology / Q000378:metabolism; D000072377:Syk Kinase; D000099181:Dectin-1
chemical_list: D058847:Inflammasomes; D047908:Intracellular Signaling Peptides and Proteins; D037181:Lectins, C-Type; D011505:Protein-Tyrosine Kinases; D000072377:Syk Kinase; C546929:CLEC7A protein, human; D000099181:Dectin-1; C000606896:SYK protein, human