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Fungal polysaccharides from Inonotus obliquus are agonists for Toll-like receptors and induce macrophage anti-cancer
Christian Winther Wold1, Panagiotis F Christopoulos2, Maykel A Arias3
1Section for Pharmaceutical Chemistry, Department of Pharmacy, University of Oslo, Oslo, Norway. christianwintherwold@gmail.com.
Abstract:
Fungal polysaccharides can exert immunomodulating activity by triggering pattern recognition receptors (PRRs) on innate immune cells such as macrophages. Here, we evaluate six polysaccharides isolated from the medicinal fungus Inonotus obliquus for their ability to activate mouse and human macrophages. We identify two water-soluble polysaccharides, AcF1 and AcF3, being able to trigger several critical antitumor functions of macrophages. AcF1 and AcF3 activate macrophages to secrete nitric oxide and the pro-inflammatory cytokines tumor necrosis factor-α (TNF-α) and interleukin-6 (IL-6). Combined with interferon-γ, the fungal polysaccharides trigger high production of IL-12p70, a central cytokine for antitumor immunity, and induce macrophage-mediated inhibition of cancer cell growth in vitro and in vivo. AcF1 and AcF3 are strong agonists of the PRRs Toll-like receptor 2 (TLR2) and TLR4, and weak agonists of Dectin-1. In comparison, two prototypical particulate β-glucans, one isolated from I. obliquus and one from Saccharomyces cerevisiae (zymosan), are agonists for Dectin-1 but not TLR2 or TLR4, and are unable to trigger anti-cancer functions of macrophages. We conclude that the water-soluble polysaccharides AcF1 and AcF3 from I. obliquus have a strong potential for cancer immunotherapy by triggering multiple PRRs and by inducing potent anti-cancer activity of macrophages.
Insights
Two polysaccharides from the medicinal fungus Inonotus obliquus, AcF1 and AcF3, activate macrophages to fight cancer. These compounds show potential for cancer immunotherapy by triggering pattern recognition receptors (PRRs).
Area of Science:
- Immunology
- Mycology
- Cancer Research
Background:
- Fungal polysaccharides modulate immune responses by activating pattern recognition receptors (PRRs) on innate immune cells.
- Macrophages play a crucial role in innate immunity and cancer surveillance.
Purpose of the Study:
- To evaluate the immunomodulatory and anti-cancer activities of polysaccharides isolated from Inonotus obliquus.
- To identify specific polysaccharides that activate macrophages and trigger anti-tumor functions.
Main Methods:
- Six polysaccharides from Inonotus obliquus were isolated and tested for their ability to activate mouse and human macrophages.
- Macrophage activation was assessed by measuring the secretion of nitric oxide, pro-inflammatory cytokines (TNF-α, IL-6), and IL-12p70.
- Macrophage-mediated anti-cancer activity was evaluated in vitro and in vivo.
- The interaction of polysaccharides with pattern recognition receptors (PRRs) such as TLR2, TLR4, and Dectin-1 was investigated.
Main Results:
- Two water-soluble polysaccharides, AcF1 and AcF3, significantly activated macrophages.
- AcF1 and AcF3 induced the secretion of nitric oxide, TNF-α, and IL-6.
- In combination with interferon-γ, AcF1 and AcF3 promoted high IL-12p70 production and inhibited cancer cell growth.
- AcF1 and AcF3 acted as strong agonists for Toll-like receptor 2 (TLR2) and Toll-like receptor 4 (TLR4), and weak agonists for Dectin-1.
- Particulate β-glucans from I. obliquus and Saccharomyces cerevisiae activated Dectin-1 but not TLR2 or TLR4, and did not trigger anti-cancer functions.
Conclusions:
- Water-soluble polysaccharides AcF1 and AcF3 from Inonotus obliquus possess potent anti-cancer properties.
- These polysaccharides activate macrophages through multiple PRRs, including TLR2 and TLR4.
- AcF1 and AcF3 demonstrate significant potential for development as immunotherapeutic agents in cancer treatment.
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