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

PLoS One. 2015 Sep 2;10(9):e0137129. doi: 10.1371/journal.pone.0137129. eCollection 2015.


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.

Publication types

  • Research Support, N.I.H., Extramural

MeSH terms

  • Animals
  • Bacterial Infections / genetics
  • Bacterial Infections / metabolism*
  • Carrier Proteins / genetics
  • Carrier Proteins / metabolism*
  • Cytokines / metabolism
  • Epithelium, Corneal / metabolism*
  • Gene Expression
  • Gene Targeting*
  • Inflammation Mediators / metabolism
  • Keratitis / genetics
  • Keratitis / metabolism*
  • Mice
  • Mice, Inbred BALB C
  • Mice, Knockout
  • N-Acetylmuramoyl-L-alanine Amidase / genetics
  • N-Acetylmuramoyl-L-alanine Amidase / metabolism*


  • Carrier Proteins
  • Cytokines
  • Inflammation Mediators
  • Pglyrp3 protein, mouse
  • Pglyrp4 protein, mouse
  • N-Acetylmuramoyl-L-alanine Amidase
  • Pglyrp2 protein, mouse