Differential expression of antimicrobial peptides in human fungal keratitis

Abstract

AIM: To analyze a series of antimicrobial peptides (AMPs) in corneal tissue from individuals with fungal keratitis (FK) during the active phase of the fungus infection and after healing. METHODS: Patients undergone lamellar keratoplasty for the treatment of severe FK or corneal scar had their corneal buttons sampled. Quantitative real-time polymerase chain reaction (PCR) was used to ascertain the gene expression of human beta-defensin (HBD)-1, -2, -3, -9, S100A7, 8, 9, and LL-37. RESULTS: All AMPs’ messenger ribonucleic acid (mRNA) expression was considerably elevated in all samples (n=12). In contrast to controls, where HBD-2, -3, and S100A7 mRNAs were expressed at very low levels, it was discovered that HBD-1, -9, S100A8, S100A9, and LL-37 were constitutively expressed in all healed samples (n=4). HBD-1, -2 -3, S100A7, and LL-37 mRNAs were significantly increased in all active FK samples (n=8). The levels of HBD-9, S100A8, and S100A9 mRNAs were moderately upregulated in all active FK samples. Subgroup comparison showed that HBD-2 was significantly increased in Fusarium keratitis samples (n=5), and LL-37 mRNAs were significantly enhanced in Aspergillus keratitis samples (n=3). Whereas there was not significantly increased of HBD-1, -3, -9, S100A7, 8, 9 mRNA in Aspergillus keratitis samples compared with Fusarium keratitis samples. CONCLUSION: AMPs expression is increased in active FK, but not all AMPs are equally expressed. HBD-2 and LL-37 expression levels are the highest, showing some specificity of AMP expression related to FK. Human AMPs, particularly HBD-2 may play a significant role in Fusarium keratitis and LL-37 might be the key player in Aspergillus keratitis.

Immune Mechanisms of Filamentous Fungal Keratitis

“…In addition, on the ocular surface, there are a large number of substances with antiinflammatory and bactericidal effects, such as secretory IgA, mucin glycoproteins, and antimicrobial peptides, such as human β-defensin 2 (HBD-2) and LL-37 (cathelicidin), which have been found to be particularly elevated in filamentous fungal keratitis [24,25]. Wang et al recently suggested that these antimicrobial peptides may not be equally expressed in fungal keratitis since they found HBD-2 mRNAs to be more elevated in Fusarium keratitis while LL-37 mRNAs in cases of Aspergillus keratitis [17].…”

“…The cornea is therefore a natural barrier that prevents pathogens from further invading its stroma. Furthermore, the expression of antimicrobial peptides (AMPs), such as human β-defensin (HBD) and LL-37 (cathelicidin protein) by the epithelium, also contributes to this [17,18]. Moreover, the constant flow of tears can naturally clean the corneal surface from microorganisms and other substances.…”

“…The increased level of AMPs during fungal keratitis results in the immediate killing of microorganisms and the promotion of other antifungal mechanisms such as increased infiltration by neutrophils [17].…”