IL-36γ promotes anti-fungi immunity by regulating macrophage function in the Aspergillus fumigatus keratitis.

PURPOSE: To explore the role of IL-36γ in corneas infected by Aspergillus fumigatus (A. fumigatus).

METHODS

Expression of IL-36γ was analyzed in 23 fungal keratitis and 8 healthy donor corneas. C57BL/6 mice corneas were infected with A. fumigatus and IL-36 cytokines expression was assessed. Then, C57BL/6 mice with A. fumigatus keratitis were treated with rmIL-36γ or IL-36γ siRNA to assess CCL-2 expression and macrophage infiltration. In vitro, RAW264.7 macrophages were stimulated with A. fumigatus and pretreated separately with Dectin-1 neutralizing antibody, rmIL-36γ, or IL-36γ siRNA. Expression of IL-6, autophagy-related proteins (LC3-II, ATG7, p62), and phagocytic activity were measured.

RESULTS

A. fumigatus infection upregulated IL-36γ. rmIL-36γ increased CCL-2 and promoted macrophage recruitment, while IL-36γ siRNA suppressed these responses. In RAW264.7 macrophages, A. fumigatus upregulated IL-6 via the Dectin-1/IL-36γ/IL-36R pathway. Furthermore, IL-36γ boosted phagocytosis. IL-36γ not only promotes autophagosome accumulation but also facilitates autophagic flux.

CONCLUSION

IL-36γ enhances anti-fungal immunity in the cornea during A. fumigatus infection by modulating macrophage function.