| First Author | Ramadan A | Year | 2023 |
| Journal | Invest Ophthalmol Vis Sci | Volume | 64 |
| Issue | 2 | Pages | 11 |
| PubMed ID | 36749596 | Mgi Jnum | J:355414 |
| Mgi Id | MGI:7436829 | Doi | 10.1167/iovs.64.2.11 |
| Citation | Ramadan A, et al. (2023) The NLRP3 Inflammasome Is Required for Protection Against Pseudomonas Keratitis. Invest Ophthalmol Vis Sci 64(2):11 |
| abstractText | PURPOSE: The current study was designed to examine the role of the NLRP3 inflammasome pathway in the clearance of Pseudomonas aeruginosa (PA) infection in mouse corneas. METHODS: Corneas of wild type and NLRP3-/- mice were infected with PA. The severity of bacterial keratitis was graded on days 1 and 3 post-infection by slit lamp, and then corneas were harvested for: (i) bacterial enumeration, (ii) immune cell analysis by flow cytometry, (iii) immunoblotting analysis of cleaved caspase-1 and IL-1beta, and (iv) IL-1beta quantification by ELISA. In parallel experiments, severity of keratitis was examined in the wild-type mice receiving a subconjunctival injection of a highly selective NLRP3 inhibitor immediately prior to infection. RESULTS: Compared to wild type mice, NLRP3-/- mice exhibited more severe infection, as indicated by an increase in opacity score and an increase in bacterial load. The hallmark of inflammasome assembly is the activation of proinflammatory caspase-1 and IL-1beta by cleavage of their precursors, pro-caspase-1 and pro-IL-1beta, respectively. Accordingly, increased severity of infection in the NLRP3-/- mice was associated with reduced levels of cleaved forms of caspase-1 and IL-1beta and reduced IL-1beta+ neutrophil infiltration in infected corneas. Likewise, corneas of mice receiving subconjunctival injections of NLRP3 inhibitor exhibited increased bacterial load, and reduced IL-1beta expression. CONCLUSIONS: Activation of NLRP3 pathway is required for the clearance of PA infection in mouse corneas. |
