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Published on: January 7, 2019
Dectin-1 promotes fungicidal activity of human neutrophils
Adam D Kennedy1, Janet A Willment, David W Dorward
1Laboratory of Human Bacterial Pathogenesis, Rocky Mountain Laboratories, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Hamilton, MT 59840, USA.
Abstract:
Human polymorphonuclear leukocytes (PMN) are a first line of defense against fungal infections. PMN express numerous pattern recognition receptors (PRR) that facilitate identification of invading microorganisms and ultimately promote resolution of disease. Dectin-1 (beta-glucan receptor) is a PRR expressed on several cell types and has been studied on monocytes and macrophages. However, the role played by dectin-1 in the recognition and killing of fungi by PMN is unknown. We investigated the ability of dectin-1 to mediate human PMN phagocytosis and fungicidal activity. Dectin-1 was expressed on the surface of PMN from all subjects tested (n=29) and in an intracellular compartment that co-sedimented with azurophilic granules in Percoll density gradients. Soluble beta-glucan and mAb GE2 (anti-dectin-1) inhibited binding and phagocytosis of zymosan by human PMN (e.g., ingestion was inhibited 40.1% by 30 min, p<0.001), and blocked reactive oxygen species production. Notably, soluble beta-glucan and GE2 inhibited phagocytosis and killing of Candida albicans by PMN (inhibition of killing was 54.8% for beta-glucan and 36.2% for GE2, p<0.01). Our results reveal a mechanism whereby PMN dectin-1 plays a key role in the recognition and killing of fungal pathogens by the innate immune system.
Insights
Human polymorphonuclear leukocytes (PMN) utilize dectin-1, a pattern recognition receptor, to identify and eliminate fungal pathogens. This study reveals dectin-1
Area of Science:
- Immunology
- Cell Biology
- Microbiology
Background:
- Human polymorphonuclear leukocytes (PMN) are crucial for innate immunity against fungal infections.
- Pattern recognition receptors (PRR) on PMN mediate pathogen recognition.
- The role of dectin-1 (a beta-glucan receptor) in PMN function against fungi remains unclear.
Purpose of the Study:
- To investigate the expression and function of dectin-1 in human PMN.
- To determine if dectin-1 mediates phagocytosis and fungicidal activity of PMN against fungi.
Main Methods:
- Dectin-1 expression analysis on human PMN.
- Functional assays using zymosan and Candida albicans.
- Inhibition studies with soluble beta-glucan and anti-dectin-1 antibody (mAb GE2).
- Measurement of phagocytosis, reactive oxygen species production, and fungal killing.
Main Results:
- Dectin-1 is expressed on the surface and within intracellular granules of human PMN.
- Soluble beta-glucan and mAb GE2 significantly inhibited zymosan binding, phagocytosis, and reactive oxygen species production by PMN.
- Both soluble beta-glucan and mAb GE2 markedly reduced PMN phagocytosis and killing of Candida albicans.
Conclusions:
- Dectin-1 is expressed on human PMN and plays a significant role in fungal recognition.
- PMN dectin-1 mediates key functions in phagocytosis and killing of fungal pathogens.
- Dectin-1 represents a critical component of the innate immune response to fungal infections.
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