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Updated: May 21, 2026
Recurrent Herpetic Stromal Keratitis in Mice, a Model for Studying Human HSK
Published on: December 18, 2012
Loss of Streptococcus pneumoniae iga Causes More Severe Keratitis in Mice
Mary A Carr1, Eva M Bengtén1,2, Mary E Marquart1,2
1Department of Cell and Molecular Biology, University of Mississippi Medical Center, Jackson, Mississippi, United States.
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.
Insights
The absence of Streptococcus pneumoniae IgA1 protease increases bacterial survival and corneal inflammation in a mouse keratitis model. This finding suggests IgA1 protease is crucial for S. pneumoniae virulence in ocular infections.
Area of Science:
- Ophthalmology
- Microbiology
- Immunology
Background:
- Streptococcus pneumoniae causes various diseases, including lung and ocular infections.
- S. pneumoniae IgA1 protease cleaves human IgA1, a key mucosal defense protein.
- While IgA1 protease is vital for pneumonia virulence, its role in ocular infections was unstudied.
Purpose of the Study:
- To investigate the role of Streptococcus pneumoniae IgA1 protease in the mouse keratitis model.
- To determine if the gene encoding IgA1 protease is required for virulence in ocular surface infections.
Main Methods:
- A/J mice with scratched ocular surfaces were infected with S. pneumoniae D39 or its IgA1 protease mutant (D39Δiga).
- Disease severity and bacterial loads were assessed at 8 and 24 hours post-infection.
- Cytokine/chemokine levels and neutrophil infiltration in corneas were quantified.
Main Results:
- Mice infected with the IgA1 protease mutant (D39Δiga) showed significantly higher bacterial loads and clinical scores at 24 hours.
- Corneas infected with D39Δiga had increased levels of inflammatory cytokines and chemokines at 8 hours.
- A higher number of neutrophils infiltrated corneas infected with D39Δiga at 24 hours.
Conclusions:
- Absence of S. pneumoniae IgA1 protease enhances bacterial survival on the mouse ocular surface.
- IgA1 protease deficiency leads to increased corneal inflammation.
- The study highlights the importance of IgA1 protease in S. pneumoniae ocular virulence.
