Galectin-3 plays an important pro-inflammatory role in A. fumigatus keratitis by recruiting neutrophils and activating p38 in neutrophils

Int Immunopharmacol. 2021 Apr 29;97:107706. doi: 10.1016/j.intimp.2021.107706. Online ahead of print.


PURPOSE: To determine the role of galectin-3 (Gal-3) in cornea infected by Aspergillus fumigatus (A. fumigatus).

METHODS: Gal-3 was tested in normal and infected corneas of C57BL/6 mice. Mice corneas were pretreated with or without rmGal-3 or Gal-3 siRNA and infected with A. fumigatus. Recombinant mouse (rm) Gal-3 stimulated polymorphonuclear neutrophilic leukocytes (PMNs). PMNs were stimulated with 75% ethanol-killed A. fumigatus with or without pretreatment of Gal-3 siRNA. Disease severity was documented by clinical score and photographs with a slit lamp. PCR, Western blot, and ELISA tested expression of Gal-3, interleukin (IL)-1β, IL-6, macrophage inflammatory protein 2 (MIP-2) and p-p38. PMNs infiltration was assessed by flow cytometry and myeloperoxidase (MPO) assay.

RESULTS: Gal-3 expression was significantly elevated by A. fumigatus in mice corneas. rmGal-3 treatment increased clinical scores, PMNs infiltration, and cytokines expression, which were decreased by Gal-3 siRNA treatment. In PMNs, Gal-3 expression was also significantly increased by A. fumigatus. The rmGal-3 treatment upregulated proinflammatory cytokines secretion and p-p38 expression, which was significantly inhibited by Gal-3 siRNA.

CONCLUSION: These data proved that A. fumigatus increased Gal-3 expression and elevated disease clinical scores, PMNs infiltration and cytokines expression through Gal-3. In PMNs, A. fumigatus upregulated IL-1β and IL-6 secretion through the Gal-3 / p38 pathway.

PMID:33933850 | DOI:10.1016/j.intimp.2021.107706

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