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From the Department of Anatomy and Cell Biology, Wayne State University School of Medicine, Detroit, Michigan.
PURPOSE. To compare the early gene expression pattern of normal versus Pseudomonas aeruginosa–infected corneas in resistant (cornea heals) versus susceptible (cornea perforates) mice.
METHODS. A microarray analysis of normal versus postinfection (PI) day 1 BALB/c and B6 corneas was performed with a murine gene microarray. Real-time RT-PCR was used to confirm the microarray pattern selectively.
RESULTS. The 1257 regulated transcripts detected were organized into nine clusters by a self-organizing map (SOM) algorithm according to their different behavior in each mouse group. At least three groups of genes associated with a CD4+ T-cell type-1 (Th1) immune response and three clusters linked with a type-2 T-cell (Th2) response were identified. Biological categorization revealed that the cornea of B6 mice showed a dominant type-1–like immune response profile, whereas BALB/c mice showed a dominant type-2–like profile. In addition, expression of several genes that promote apoptosis (e.g., caspase-9) was upregulated in BALB/c mouse cornea, whereas genes with apoptosis-inhibiting activity (e.g., BCL2) were significantly upregulated in B6 mouse cornea. The infected cornea of BALB/c mice also showed increased gene expression of factors associated with matrix remodeling and tissue repair (e.g., tissue inhibitor of matrix metalloproteinase [TIMP-2] and epidermal growth factor [EGF]) and/or bacterial killing (e.g., inducible nitric oxide synthase [iNOS]).
CONCLUSIONS. The data provide new insight into biological processes involved in Pseudomonas aeruginosa keratitis and confirm that B6 mice are Th1 and BALB/c mice are Th2 cytokine responsive to bacterial antigen early after challenge with P. aeruginosa.
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