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Shukti Chakravarti, Ranjita N Gowda, Sudarshan Punglay, Wai-Hong Wu, Abdel R Hamad; Peptidoglycan recognition protein 2 (Pglyrp 2) exacerbates Pseudomonas aeruginosa keratitis in a mouse model.. Invest. Ophthalmol. Vis. Sci. 2014;55(13):1463.
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Others and we detected four mammalian peptidoglycan recognition proteins, Pglyrp1-4, in the human and mouse cornea. We reported earlier that Pglyrp1-/- mice were more susceptible to Pseudomonas aeruginosa keratitis, indicating a protective role for this antimicrobial protein. Here we investigated P. aeruginosa keratitis in Pglyrp 2-/-, Pglyrp 3-/-, Pglyrp 4-/- and wild type Balb/c (WT) mice to determine the role of Pglyrp2-4 in ocular surface defense.
One eye each, in 6-8 week old mice were scarified and infected with approximately 50,000 cfu P. aeruginosa (ATCC19660). Both males and females (n=6-9 per genotype), gender matched within an experiment were used. Five independent keratitis experiments/genotype were conducted. Visual disease scores were given in a blinded manner 1 and 2 days post infection. Viable bacterial counts and IL-12, TNF-α, IFN-γ, CCL2, IL-6 and IL-10 levels (Cytometric Bead Array, BD Biosciences) were measured in whole eye homogenates. Expression of Pglyrp1-4 was determined by qRTPCR from total RNA extracts of uninfected and infected eyes of WT and Pglyrp null mice.
The Pglyrp 2-/- mice, males in particular, showed consistently lower disease scores and bacterial yield compared to WT (p= 0.02 and p= 0.004 for disease score and CFU, respectively). The Pglyrp 4-/- mice also manifested reduced disease score and bacterial load without reaching statistical significance. Induction of TNF-α in infected Pglyrp 2-/- eyes was lower than that of WT mice. The Pglyrp 3-/- mice showed no significant differences in disease scores, bacterial yield or induction of cytokines compared to WT, and expression of Pglyrp4 was elevated. Pglyrp1 expression was constitutively high in the WT and Pglyrp2-4 null mouse eyes, while Pglyrp2 was induced in WT infected eyes.
In addition to being an amidase that hydrolyses peptidoglycans, Pglyrp2 is known to promote pro-inflammatory signals. Our results indicate that Pglyrp2 may be counter-productive to clearing Pseudomonas infections, and its expression tightly regulated during infections and inflammation.
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