Abstract
Purpose: :
To investigate the genetic expression profile during the early stage of posttraumatic Candida albicans keratitis in inbred mice.
Methods: :
Following unilateral superficial corneal scarification of BALB/c mice, eyes were topically exposed to wild-type C. albicans (SC5314) or were mock-inoculated. After 24 hours, corneas were excised and pooled in sets of five for RNA extraction. Each experimental group was examined in triplicate by microarray using Affymetrix GeneChips® Mouse Expression Set 430, which screens for 45,101 potential murine gene transcripts. A twofold or greater difference (P < 0.05) between fungal-infected corneas compared to mock-infected controls was set as the cutoff criteria for significance. Real-time PCR was used to confirm selective gene expression patterns.
Results: :
Among all tested murine genes 1,514 (3.4%) transcripts changed significantly during early infection. Inhibitory regulators of the Janus kinase/signal transducers and activators of transcription (JAK/STAT) pathway were significantly altered (P < .0001), including suppressors of cytokine signaling (SOCS3 and SOCS7). Genes involved in interleukin-2, interleukin-4, granulocyte-macrophage-colony stimulating factor, epidermal growth factor, and vascular endothelial growth factor pathways were significantly upregulated (P < .005). Fungal infected corneas also had increased gene expression by tenfold for tumor necrosis factor-alpha and by twofold for matrix metalloproteinase 9.
Conclusions: :
Cytokine signaling within the cornea, including genetic downregulation of the JAK/STAT pathway and increased expression of genes regulating interleukins and growth factors, occurred during the initial pathogenesis of experimental C. albicans keratitis.
Keywords: fungal disease • keratitis • microbial pathogenesis: experimental studies