Journal
JOURNAL OF IMMUNOLOGY
Volume 192, Issue 12, Pages 5952-5962Publisher
AMER ASSOC IMMUNOLOGISTS
DOI: 10.4049/jimmunol.1303213
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Funding
- Academy of Finland [125826, 135628, 140950]
- Finnish Work Environment Fund
- Sigrid Juselius Foundation
- Graduate School in Environmental Health 'SYTYKE'
- Helsinki Biomedical Graduate School
- Viikki Doctoral Programme in Molecular Biosciences
- Nummela Foundation
- Finnish Medical Society (Finska lakaresallskapet)
- Academy of Finland (AKA) [140950, 135628, 140950, 135628] Funding Source: Academy of Finland (AKA)
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Dectin-1 is a membrane- bound pattern recognition receptor for b-glucans, which are the main constituents of fungal cell walls. Detection of b-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.
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