Related Experiment Videos
Role of complement in murine corneal infection caused by Pseudomonas aeruginosa
Abstract:
The role of complement components C3 and C5 was examined in murine corneal infection induced by Pseudomonas aeruginosa. DBA/2 and Swiss-Webster mice are naturally resistant to experimental P. aeruginosa corneal infection. Mice of these two strains are able to restore a clear cornea within 4-6 weeks following Pseudomonas corneal challenge and are genetically deficient in the fifth component of complement. In contrast, ocular infection of congenic C5-deficient B10.D2o/Sn or normocomplementemic B10.D2n/Sn mice results in an identical pattern of susceptibility in which corneal perforation and phthisis bulbi occur. Taken together, these results indicate that C5 plays little or no role in susceptibility or resistance to Pseudomonas eye infection. In contrast, depletion of C3 in normally resistant DBA/2 mice using cobra venom factor (CoVF) diminishes the ability of these mice to restore a clear cornea following Pseudomonas infection. A single inoculation of CoVF, 24 hours prior to ocular challenge, is as effective in altering the response of DBA/2 mice as is continuous depletion of C3 during the course of infection using multiple inoculations of CoVF. Mice that are unable to clear Pseudomonas ocular infection following CoVF treatment regain this ability when the contralateral eye is infected after recovery of normal levels of C3. Depletion of C3 by CoVF treatment of DBA/2 mice, which had previously restored a clear cornea following Pseudomonas eye infection, again renders these mice susceptible.
Insights
Complement component C3, not C5, is crucial for clearing Pseudomonas aeruginosa corneal infections in mice. Depleting C3 impairs recovery, highlighting its role in resistance to bacterial keratitis.
Area of Science:
- Immunology
- Ophthalmology
- Microbiology
Background:
- Pseudomonas aeruginosa is a common cause of bacterial keratitis.
- The role of complement system components in P. aeruginosa corneal infection is not fully understood.
- Murine models are used to study host-pathogen interactions in ocular infections.
Purpose of the Study:
- To investigate the role of complement components C3 and C5 in Pseudomonas aeruginosa murine corneal infection.
- To determine the impact of C3 and C5 deficiency on the outcome of P. aeruginosa keratitis.
- To elucidate the mechanisms of resistance and susceptibility in P. aeruginosa ocular infections.
Main Methods:
- Corneal infection model using Pseudomonas aeruginosa in DBA/2 and Swiss-Webster mice.
- Utilized genetically C5-deficient mice (B10.D2o/Sn) and normocomplementemic controls (B10.D2n/Sn).
- Depletion of C3 using cobra venom factor (CoVF) in resistant DBA/2 mice.
Main Results:
- C5-deficient mice exhibited similar susceptibility to P. aeruginosa corneal infection as normal mice.
- Depletion of C3 in DBA/2 mice significantly impaired their ability to clear the infection and restore corneal clarity.
- Transient C3 depletion prior to infection was as effective in increasing susceptibility as continuous depletion.
- Mice treated with CoVF regained the ability to clear infection after C3 levels normalized.
Conclusions:
- Complement component C5 plays a minimal role in resistance or susceptibility to P. aeruginosa corneal infection.
- Complement component C3 is essential for effective clearance of P. aeruginosa from the cornea.
- Targeting C3 may offer therapeutic strategies for managing severe bacterial keratitis.