Dectin-1 Controls TLR9 Trafficking to Phagosomes Containing β-1,3 Glucan

J Immunol. 2016 Mar 1;196(5):2249-61. doi: 10.4049/jimmunol.1401545. Epub 2016 Feb 1.


Dectin-1 and TLR9 play distinct roles in the recognition and induction of innate immune responses to Aspergillus fumigatus and Candida albicans. Dectin-1 is a receptor for the major fungal cell wall carbohydrate β-1,3 glucan that induces inflammatory cytokines and controls phagosomal maturation through spleen tyrosine kinase activation. TLR9 is an endosomal TLR that also modulates the inflammatory cytokine response to fungal pathogens. In this study, we demonstrate that β-1,3 glucan beads are sufficient to induce dynamic redistribution and accumulation of cleaved TLR9 to phagosomes. Trafficking of TLR9 to A. fumigatus and C. albicans phagosomes requires Dectin-1 recognition. Inhibition of phagosomal acidification blocks TLR9 accumulation on phagosomes containing β-1,3 glucan beads. Dectin-1-mediated spleen tyrosine kinase activation is required for TLR9 trafficking to β-1,3 glucan-, A. fumigatus-, and C. albicans-containing phagosomes. In addition, Dectin-1 regulates TLR9-dependent gene expression. Collectively, our study demonstrates that recognition of β-1,3 glucan by Dectin-1 triggers TLR9 trafficking to β-1,3 glucan-containing phagosomes, which may be critical in coordinating innate antifungal defense.

Publication types

  • Research Support, N.I.H., Extramural

MeSH terms

  • Animals
  • Aspergillus fumigatus / immunology
  • Candida albicans / immunology
  • Cell Line
  • Cluster Analysis
  • Gene Expression Profiling
  • Gene Expression Regulation
  • Gene Knockout Techniques
  • Humans
  • Hydrogen-Ion Concentration
  • Intracellular Signaling Peptides and Proteins / metabolism
  • Lectins, C-Type / metabolism*
  • Macrophages / immunology
  • Macrophages / metabolism
  • Macrophages / microbiology
  • Mice
  • Models, Biological
  • Phagocytosis
  • Phagosomes / metabolism*
  • Protein Transport
  • Protein-Tyrosine Kinases / metabolism
  • Signal Transduction
  • Syk Kinase
  • Toll-Like Receptor 9 / genetics
  • Toll-Like Receptor 9 / metabolism*
  • beta-Glucans / metabolism*


  • Intracellular Signaling Peptides and Proteins
  • Lectins, C-Type
  • Toll-Like Receptor 9
  • beta-Glucans
  • dectin 1
  • Protein-Tyrosine Kinases
  • SYK protein, human
  • Syk Kinase
  • Syk protein, mouse