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http://purl.uniprot.org/citations/26332373http://www.w3.org/1999/02/22-rdf-syntax-ns#typehttp://purl.uniprot.org/core/Journal_Citation
http://purl.uniprot.org/citations/26332373http://www.w3.org/2000/01/rdf-schema#comment"

Purpose

Functions 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.

Methods

Wild 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.

Results

The 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.

Conclusions

Efficient 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."xsd:string
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http://purl.uniprot.org/citations/26332373http://purl.uniprot.org/core/author"Foster J.W."xsd:string
http://purl.uniprot.org/citations/26332373http://purl.uniprot.org/core/author"Chakravarti S."xsd:string
http://purl.uniprot.org/citations/26332373http://purl.uniprot.org/core/author"Cope L."xsd:string
http://purl.uniprot.org/citations/26332373http://purl.uniprot.org/core/author"Redfern R."xsd:string
http://purl.uniprot.org/citations/26332373http://purl.uniprot.org/core/author"Pinglay S."xsd:string
http://purl.uniprot.org/citations/26332373http://purl.uniprot.org/core/author"Lema C."xsd:string
http://purl.uniprot.org/citations/26332373http://purl.uniprot.org/core/author"Gowda R.N."xsd:string
http://purl.uniprot.org/citations/26332373http://purl.uniprot.org/core/author"Frikeche J."xsd:string
http://purl.uniprot.org/citations/26332373http://purl.uniprot.org/core/date"2015"xsd:gYear
http://purl.uniprot.org/citations/26332373http://purl.uniprot.org/core/name"PLoS One"xsd:string
http://purl.uniprot.org/citations/26332373http://purl.uniprot.org/core/pages"e0137129"xsd:string
http://purl.uniprot.org/citations/26332373http://purl.uniprot.org/core/title"Functions of Peptidoglycan Recognition Proteins (Pglyrps) at the Ocular Surface: Bacterial Keratitis in Gene-Targeted Mice Deficient in Pglyrp-2, -3 and -4."xsd:string
http://purl.uniprot.org/citations/26332373http://purl.uniprot.org/core/volume"10"xsd:string
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