Dectin-1 pathway activates robust autophagy-dependent unconventional protein secretion in human macrophages

J Immunol. 2014 Jun 15;192(12):5952-62. doi: 10.4049/jimmunol.1303213. Epub 2014 May 7.

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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Autophagy / immunology*
  • Female
  • Gene Expression Regulation / immunology*
  • Humans
  • Immunity, Innate*
  • Inflammasomes / immunology*
  • Inflammasomes / metabolism
  • Intracellular Signaling Peptides and Proteins / immunology
  • Intracellular Signaling Peptides and Proteins / metabolism
  • Lectins, C-Type / immunology*
  • Macrophages / immunology*
  • Macrophages / metabolism
  • Male
  • Mycoses / immunology
  • Mycoses / metabolism
  • Protein-Tyrosine Kinases / immunology
  • Protein-Tyrosine Kinases / metabolism
  • Syk Kinase

Substances

  • CLEC7A protein, human
  • Inflammasomes
  • Intracellular Signaling Peptides and Proteins
  • Lectins, C-Type
  • Protein-Tyrosine Kinases
  • SYK protein, human
  • Syk Kinase

Associated data

  • GEO/GSE32282