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

Sci Rep. 2024 Nov 16;14(1):28278. doi: 10.1038/s41598-024-79837-7.

Abstract

We focused on the possibility that pathogenic microorganisms might produce immune suppressors to evade the action of immune cells. Based on this possibility, we have recently developed new co-culture method of pathogenic actinomyces and immune cells, however, the interaction mechanism between pathogens and cells was still unclear. In this report, co-culturing pathogenic fungi and immune cells were investigated. Pathogenic fungus Aspergillus terreus IFM 65899 and THP-1 cells were co-cultured and isolated a co-culture specific compound, butyrolactone Ia (1). 1 inhibits the production of nitric oxide by RAW264 cells and exhibits regulatory effects on autophagy, suggesting 1 plays a defensive role in the response of A. terreus IFM 65899 to immune cells. Furthermore, dialysis experiments and micrographs indicated that "physical interaction" between A. terreus IFM 65899 and THP-1 cells may be required for the production of 1. This is the first report of co-culture method of fungi with immune cells and its interaction mechanism.

MeSH terms

  • 4-Butyrolactone* / analogs & derivatives
  • 4-Butyrolactone* / metabolism
  • Animals
  • Aspergillus* / metabolism
  • Autophagy
  • Biological Products / pharmacology
  • Coculture Techniques*
  • Humans
  • Mice
  • Nitric Oxide* / metabolism
  • RAW 264.7 Cells
  • THP-1 Cells

Substances

  • 4-Butyrolactone
  • butyrolactone I
  • Nitric Oxide
  • Biological Products

Supplementary concepts

  • Aspergillus terreus