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Dectin-1 Controls TLR9 Trafficking to Phagosomes Containing β-1,3 Glucan
Nida S Khan1, Pia V Kasperkovitz2, Allison K Timmons3
1Division of Infectious Diseases, Department of Medicine, Massachusetts General Hospital, Boston, MA 02114; Biomedical Engineering and Biotechnology, University of Massachusetts, Lowell, MA 01854;
Journal of Immunology (Baltimore, Md. : 1950)
|February 3, 2016
Summary
Dectin-1 receptor activation by fungal beta-1,3 glucans directs Toll-like receptor 9 (TLR9) to phagosomes. This Dectin-1-dependent TLR9 trafficking is crucial for innate immune responses against fungal pathogens.
Area of Science:
- Immunology
- Microbiology
- Cell Biology
Background:
- Dectin-1 and Toll-like receptor 9 (TLR9) are key pattern recognition receptors in innate immunity against fungal pathogens like Aspergillus fumigatus and Candida albicans.
- Dectin-1 recognizes beta-1,3 glucan, a major fungal cell wall component, and initiates inflammatory responses.
- TLR9 is an endosomal receptor that also contributes to antifungal immunity by modulating cytokine production.
Purpose of the Study:
- To investigate the interplay between Dectin-1 and TLR9 in the context of fungal recognition and innate immune signaling.
- To determine if Dectin-1 activation influences the localization and function of TLR9 during fungal phagocytosis.
Main Methods:
- Utilized beta-1,3 glucan beads and fungal pathogens (A. fumigatus, C. albicans) to stimulate immune cells.
- Investigated the subcellular localization of TLR9 using microscopy, focusing on phagosomal trafficking.
- Employed pharmacological inhibitors to block phagosomal acidification and spleen tyrosine kinase (Syk) activity.
- Assessed Dectin-1's role in regulating TLR9-dependent gene expression.
Main Results:
- Beta-1,3 glucan bead stimulation induced the dynamic redistribution and accumulation of cleaved TLR9 to phagosomes.
- Dectin-1 recognition was essential for TLR9 trafficking to phagosomes containing beta-1,3 glucan beads, A. fumigatus, and C. albicans.
- Inhibition of phagosomal acidification and Dectin-1-mediated Syk activation blocked TLR9 accumulation on phagosomes.
- Dectin-1 was found to regulate TLR9-dependent gene expression, highlighting its control over TLR9 signaling.
Conclusions:
- Recognition of beta-1,3 glucan by Dectin-1 triggers the trafficking of TLR9 to phagosomes containing fungal components.
- This Dectin-1-dependent TLR9 recruitment pathway is critical for coordinating innate immune defenses against fungal infections.
- The findings reveal a novel mechanism of crosstalk between Dectin-1 and TLR9 in antifungal immunity.
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