Loss of Streptococcus pneumoniae iga Causes More Severe Keratitis in Mice.

Purpose: Streptococcus pneumoniae (S. pneumoniae) causes disease in multiple body systems, including at the ocular surface and in the lungs. S. pneumoniae IgA1 protease cleaves and inactivates human IgA1, which is present in high concentrations at mucosal surfaces. Mice lack IgA1, but studies have shown that the gene encoding IgA1 protease is required for virulence in pneumonia in mice. This study aimed to determine if the gene is required for virulence in the mouse keratitis model. Methods: S. pneumoniae D39 or the isogenic IgA1 protease mutant, D39Δiga, was applied to the scratched ocular surface of A/J mice at a dose of 108 colony-forming units (CFUs). Disease severity was scored 8 and 24 hours post-infection, and the infected eyes were removed and homogenized for quantification of bacterial loads and host proteins associated with inflammation. In addition, the number of cornea-infiltrating neutrophils was quantified by flow cytometry. Results: At 24 hours post-infection, D39Δiga-infected corneas had significantly higher remaining mean bacterial loads (5.59 log10 CFU) and clinical severity scores (2.5) compared with those infected with D39 (3.01 log10 CFU and 0.812, P = 0.002 and 0.0011, respectively). At 8 hours post-infection, these corneas contained significantly greater quantities of 16 cytokines and chemokines associated with inflammation than those infected with D39 (P < 0.05). D39Δiga infected corneas also contained significantly larger quantities of neutrophils 24 hours post-infection (P = 0.0013). Conclusions: Absence of S. pneumoniae IgA1 protease enhances bacterial survival at the mouse ocular surface and contributes to corneal inflammation.