Aspergillus fumigatus triggers innate immune response via NOD1 signaling in human corneal epithelial cells

Abstract

Fungal keratitis is a serious vision-threatening disease caused by fungi after corneal epithelium damage. We have previously shown a role of cell surface TLRs in Aspergillus fumigatus (A. fumigatus) keratitis. In the present study we showed that Human telomerase-immortalized corneal epithelial cells (HCECs) exposed to A. fumigatus elicited an inflammatory response consisting in increased interleukin-6 (IL-6), IL-8 and tumor necrosis factor (TNF)-α expression and innate defense molecules hBD2 and LL37 in a time-dependent manner. In this study we further investigated the role of intracellular nucleotide-binding oligomerization domain-containing protein (NOD)-like receptors, NOD1 in innate immune and inflammatory response to A. fumigatus. We showed that NOD1 and its downstream signaling molecules RIP2 and NF-κB p65 are expressed in HCECs challenged with either NOD1 specific ligand iE-DAP or A. fumigatus. More importantly, NOD1 knockdown attenuated A. fumigatus-triggered the expression of NOD1, and downstream signaling effectors RIP2 and NF-κB p65, as well as the secretion of IL-6, IL-8 and TNF-α, and the production of hBD2 and LL37. In conclusion, our results demonstrated that NOD1 is a prominent factor of innate immune and inflammatory response in HCECs against A. fumigatus, suggesting that NOD1 might be a potential novel therapeutic target for the treatment of fungal keratitis.