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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.

plos one

Functions of Peptidoglycan Recognition Proteins (Pglyrps) at the Ocular Surface: Bacterial Keratitis in Gene-Targeted Mice Deficient in Pglyrp-2, -3 and -4