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Aspergillus terreus IFM 65899-THP-1 cells interaction triggers production of the natural product butyrolactone Ia, an immune suppressive compound

Summary

Scientists discovered that when a dangerous fungus called Aspergillus terreus is grown together with immune cells, it produces a special compound called butyrolactone Ia that helps it hide from the body’s defense system. This compound works by reducing inflammatory signals that immune cells use to fight the fungus. The research shows that direct contact between the fungus and immune cells is needed to trigger this protective compound production, suggesting the fungus responds directly to the threat of immune attack.

Background

Pathogenic microorganisms produce immune suppressors to evade immune cell action. Silent secondary metabolite-biosynthetic gene clusters in fungi typically remain inactive under standard laboratory conditions. Co-culture with immune cells may activate production of novel natural products by mimicking natural microbial interactions.

Objective

To develop a co-culture method between pathogenic fungi and immune cells for activating secondary metabolite production and identifying novel immune suppressors. To isolate and characterize co-culture specific compounds and investigate their bioactivity and production mechanisms.

Results

A co-culture-specific compound, butyrolactone Ia (1), was isolated exclusively from Aspergillus terreus IFM 65899 and THP-1 co-culture with molecular formula C23H22O7. Compound 1 inhibited nitric oxide production with IC50 of 18 µM and suppressed iNOS expression. Physical interaction between fungal and immune cells was required for compound 1 production, as dialysis separation prevented production.

Conclusion

Co-culture of pathogenic fungi with immune cells successfully activates production of novel natural products. Butyrolactone Ia exhibits immunosuppressive properties through NO inhibition and autophagy regulation. Physical cell-to-cell contact appears essential for this interaction-triggered secondary metabolite production.
  • Published in:Scientific Reports,
  • Study Type:Experimental Research,
  • Source: PMID: 39550448, DOI: 10.1038/s41598-024-79837-7
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