Glabridin Inhibits Aspergillus fumigatus Growth and Alleviate Inflammation Mediated by Dectin-2 and NLRP3 Inflammasome

Abstract

Purpose

The research was used to uncover the mechanism of glabridin in Aspergillus fumigatus keratitis in anti-fungus and anti-inflammation.

Methods

In vitro, RAW 264.7 cells were infected with A. fumigatus with incubation of glabridin in different concentrations. Real-time quantitative polymerase chain reaction (RT‑qPCR), Western blot, and enzyme-linked immunosorbent assay (ELISA) were used to assess the inflammatory severe and alternation with the intervention of Dectin-2 siRNA and glabridin. In vivo, A. fumigatus keratitis mouse models were established by spore intra-stromal injection and treated with glabridin or PBS. And disease scores, inflammatory mediators, and periodic acid-schiff (PAS) staining were exhibited to demonstrate the therapeutic efficiency of glabridin in vivo. Morphological interference assay monitored fungal germination. Scanning and transmission electron microscopy were used to observe the growth of fungi.

Results

In RAW 264.7 cells and mouse keratitis models, noncytotoxic 16 μg/mL glabridin showed significant inhibition in the expression of Dectin-2, NLRP3, Caspase-1, IL-1β, and TNF-α after A. fumigatus infection, almost similar to the intervention of Dectin-2 siRNA. PAS staining illustrated the reduced hyphal distribution in cornea stroma with glabridin treatment. Glabridin remarkably inhibited A. fumigatus growth through delaying germination and disrupting the integrity of the hyphae membrane.

Conclusion

Glabridin plays an anti-inflammatory role in A. fumigatus challenge via suppression of the Dectin-2 and NLRP3 inflammasome, and plays an anti-fungal role through delaying germination and changing the hyphal integrity.

KEY MESSAGES

• Glabridin plays an anti-inflammatory role in A. fumigatus infection of RAW264.7 cells in a concentration-dependent manner and through Dectin-2 mediation.

• Glabridin decreases fungal distribution and inflammation in mouse A. fumigatus keratitis.

• Glabridin inhibits A. fumigatus growth by delaying germination and disrupting cellular structure in vitro.

Keywords:

• Glabridin
• Aspergillus fumigatus
• fungal keratitis
• Dectin-2
• NLRP3 inflammasome

Disclosure statement

No potential conflict of interest was reported by the author(s).

Data availability statement

The raw data supporting the conclusions of this article will be made available by the authors, without undue reservation.

Additional information

Funding

This work was supported by the National Natural Science Foundation of China (Nos. 82101095, 82171029 and 81900824) and the Natural Science Foundation of Shandong Province (No. ZR2019BH004).