Abstract
PurposeFunctions of antimicrobial peptidoglycan recognition proteins (Pglyrp1-4) at the ocular surface are poorly understood. Earlier, we reported an antibacterial role for Pglyrp-1 in Pseudomonas aeruginosa keratitis. Here we investigated functions of three other related genes Pglyrp-2, -3 and -4 in a mouse model of P. aeruginosa keratitis.MethodsWild type (WT) and each of the Pglyrp-null genotypes were challenged with P. aeruginosa keratitis. The eyes were scored in a blinded manner 24 and 48h post infection. Viable bacterial counts and inflammatory factors (IL-12, TNF-α, IFN-γ, CCL2, IL-6 and IL-10) were measured in whole eye homogenates using cytometric bead arrays. Expressions of Pglyrp-1-4, mouse beta defensins (mBD)-2,-3, cathelicidin-related antimicrobial peptide (CRAMP) were determined by qRTPCR in total RNA extracts of uninfected and infected eyes of WT and each of the Pglyrp-null mouse types.ResultsThe Pglyrp-2 -/- mice showed reduced disease and lower induction of pro-inflammatory TNF-α (p = 0.02) than WT or the other Pglyrp null mice. Viable bacterial yield was significantly lower in the Pglyrp-2-/- (p = 0.0007) and the Pglyrp-4-/- (p = 0.098) mice. With regards to expression of these antimicrobial genes, Pglyrp-2 expression was induced after infection in WT mice. Pglyrp-3 expression was low before and after infection in WT mice, while Pglyrp-4 expression was slightly elevated after infection in WT, Pglyrp-2 and -3 null mice. Pglyrp-1 expression was slightly elevated after infection in all genotypes without statistical significance. Transcripts for antimicrobial peptides mBD2, mBD3 and CRAMP were elevated in infected Pglyrp-2 -/- males without statistical significance.ConclusionsEfficient resolution of keratitis in the Pglyrp-2 -/- mice may be due to a reduced pro-inflammatory microenvironment and synergistic antibacterial activities of defensins, CRAMP and Pglyrp-1. Therefore, in ocular infections the pro-inflammatory functions of Pglyrp-2 must be regulated to benefit the host.
Highlights
The peptidoglycan recognition proteins (Pglyrps) are conserved from insects to humans [1]
Efficient resolution of keratitis in the Pglyrp-2-/- mice may be due to a reduced pro-inflammatory microenvironment and synergistic antibacterial activities of defensins, cathelicidin-related antimicrobial peptide (CRAMP) and Pglyrp-1
In a follow-up study we found constitutively high expression of Pglyrp-1 in the superficial cells of the corneal epithelium in mouse and human corneas, and Pglyrp-1-/- mice challenged with P. aeruginosa keratitis showed poor bacterial clearance and resolution of keratitis [9]
Summary
The peptidoglycan recognition proteins (Pglyrps) are conserved from insects to humans [1]. In a follow-up study we found constitutively high expression of Pglyrp-1 in the superficial cells of the corneal epithelium in mouse and human corneas, and Pglyrp-1-/- mice challenged with P. aeruginosa keratitis showed poor bacterial clearance and resolution of keratitis [9]. These findings suggested a protective role for Pglyrp-1 at the ocular surface while functions of the other members, Pglyrp-2-4, at the ocular surface are largely unknown. Our study shows that disease severity is reduced with improved bacterial clearance in Pglyrp-2-/- mice that may be due to compensatory over expression of defensins (mBD2 and 3), cathelicidin-related antimicrobial peptides (Cnlp) and Pglyrp-1
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
