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TNF-alpha production in the cornea in response to Pseudomonas aeruginosa challenge
1Cooperative Research Centre for Eye Research and Technology, School of Optometry, University of New South Wales, Australia.
Abstract:
Pseudomonas aeruginosa can cause ulcerative bacterial keratitis or contact lens-induced acute red eye (CLARE) in humans. The present study used a mouse model of ocular infection and inflammation to examine the relationship between TNF-alpha and inflammation in the cornea in response to challenge with either a strain of P. aeruginosa causing keratitis or a CLARE strain. Constitutive TNF-alpha mRNA was detected in the epithelium, mainly towards the periphery. After infection with the keratitis-inducing strain (6294), TNF-alpha expression was elevated four-fold by 24 h post-challenge. No detectable induction of TNF-alpha mRNA was seen with CLARE strain (Paer1) challenge at any time point. The TNF-alpha protein production detected by ELISA showed a corresponding pattern to the mRNA expression, which also correlated with pathological changes. These results suggest that invasive strains of P. aeruginosa create greater pathological changes as a result of elevated TNF-alpha production, which contributes to inflammation during keratitis in vivo.
Insights
Elevated tumor necrosis factor-alpha (TNF-alpha) production by invasive Pseudomonas aeruginosa strains correlates with increased inflammation and pathological changes in the cornea during keratitis.
Area of Science:
- Ophthalmology
- Microbiology
- Immunology
Background:
- Pseudomonas aeruginosa is a common cause of bacterial keratitis and contact lens-induced acute red eye (CLARE).
- Tumor necrosis factor-alpha (TNF-alpha) plays a role in ocular inflammation.
Purpose of the Study:
- To investigate the role of TNF-alpha in the inflammatory response to P. aeruginosa in a mouse model of ocular infection.
- To compare the inflammatory response to a keratitis-inducing strain versus a CLARE-inducing strain of P. aeruginosa.
Main Methods:
- A mouse model of ocular infection was used.
- Mice were challenged with either a keratitis-inducing (6294) or CLARE-inducing (Paer1) strain of P. aeruginosa.
- TNF-alpha mRNA and protein expression in the cornea were measured at various time points post-infection.
- Pathological changes in the cornea were assessed.
Main Results:
- Constitutive TNF-alpha mRNA was detected in the corneal epithelium.
- Infection with the keratitis-inducing strain (6294) led to a four-fold increase in TNF-alpha mRNA expression by 24 hours.
- No significant induction of TNF-alpha mRNA was observed with the CLARE strain (Paer1).
- TNF-alpha protein levels and pathological changes correlated with mRNA expression patterns.
Conclusions:
- Invasive P. aeruginosa strains induce greater pathological changes in the cornea.
- Elevated TNF-alpha production contributes to inflammation during P. aeruginosa keratitis.
- The inflammatory response differs between keratitis-inducing and CLARE-inducing strains of P. aeruginosa.