Increased severity of Pseudomonas aeruginosa corneal infection in strains of mice designated as Th1 versus Th2 responsive

PURPOSE. Mice favoring Th1 (C57BL/6, C57BL/10, and B10.D2/nSn) versus Th2 ( BALB/c, BALB/cBy, BALB.B, and BALB.K) response development were evaluated f or their response to infection with Pseudomonas aeruginosa. This study addr esses the question of whether Th1 versus Th2 response propensity affects th e pathogenesis of bacterial keratitis in mice. METHODs. Ocular disease was determined by mean clinical score, slit lamp, p late counts, and histopathology, and antigen-specific cellular responses we re assessed by immunostaining and measurement of delayed type hypersensitiv ity (DTH). RESULTS. Strains of mice favoring Th1 (B6, BL10, and B10.D2) versus Th2 (BA LB/c, BALB/cBy, BALB.B, and BALB.K) responsiveness were infected with P. ae ruginosa. Mice favoring Th1 response development exhibited a similar course of disease and the infected eyes of all mice perforated by 7 days postinfe ction (p.i.). Strains (BALB/c, BALB/cBy, BALB.B, and BALB.K) favoring Th2 r esponse development exhibited a milder course of disease, and none of the i nfected corneas perforated at 7 days p.i. In a Th1-responsive strain (B10.D 2), positive immunostaining for CD4(+) and CD8(+) T cells was observed in t he cornea by 3 days p.i. and by 5 days p.i., respectively, some cells stain ed positively for IL2-R, indicating that the cells were activated. In contr ast, in a Th2 responder strain (BALB/c), there was no detectable positive i mmunostaining in cornea for any of the T-cell markers tested and DTH was si gnificantly elevated in B10.D2 versus BALB/c mice. CONCLUSIONS. These studies are the first to provide evidence that in P. aer uginosa ocular infection, mouse strains favoring development of a Th1-type response are susceptible (cornea perforates), whereas strains favoring Th2 response development are resistant (no corneal perforation).