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.
Yukiko Ujie  1 ,  Shun Saito  1 ,  Keisuke Fukaya  2 ,  Daisuke Urabe  2 ,  Takashi Yaguchi  3 ,  Midori A Arai  4
Affiliations
  • 1. Faculty of Science and Technology, Keio University, Yokohama, 223-8522, Japan.
  • 2. Biotechnology Research Center, Department of Biotechnology, Toyama Prefectural University, Toyama, 939-0398, Japan.
  • 3. Medical Mycology Research Center, Chiba University, Chiba, 260-8673, Japan.
  • 4. Faculty of Science and Technology, Keio University, Yokohama, 223-8522, Japan. [email protected].
PMID: 39550448 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.

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