Fungal keratitis (FK) is a keratopathy caused by pathogenic fungal infection. The
aim of this work is to explore the role of thymic stromal lymphopoietin (TSLP) in
FK. Human corneal epithelial cells (HCECs) were treated with Aspergillus fumigatus
hyphae, and we found that TSLP was highly expressed and secreted in the hyphae-treated
HCECs. Hyphae-treated HCECs or TSLP treatment enhanced the expression of caspase-1
P20, GSDMD-N (p30), IL-1 beta, and IL-18 in the human THP-1 macrophages. The influence
conferred by hyphae-treated HCECs or TSLP treatment was rescued by TSLP neutralizing
antibody or VX-765 (caspase-1 inhibitor) treatment. Moreover, TSLP treatment promoted
the expression of NLRP3, ASC, caspase-1 P20, GSDMD-N (p30), IL-1 beta, and IL-18 in
the THP-1 macrophages, which was abolished by NLRP3 knockdown. Furthermore, TSLPR
silencing suppressed the expression of NLRP3, ASC, caspase-1 P20, GSDMD-N (p30), IL-1
beta, and IL-18 in the TSLP-treated THP-1 macrophages. In conclusion, our article
confirms that Aspergillus fumigatus-stimulated HCECs induce pyroptosis of THP-1 macrophages
by secreting TSLP. TSLP/TSLPR induces caspase-1-dependent pyroptosis through activation
of NLRP3 inflammasome. Thus, our work suggests that TSLP may be a potential target
for FK treatment.
