A Novel Antimicrobial Peptidoglycan Recognition Protein in the Cornea

Overview

Journal Invest Ophthalmol Vis Sci

Specialty Ophthalmology

Date 2009 Apr 24

PMID 19387073

Citations 8

Authors

Amit Ghosh

Seakwoo Lee

Roman Dziarski

Shukti Chakravarti

Affiliations

Soon will be listed here.

Abstract

Purpose: In an earlier gene expression study, the authors identified a novel antimicrobial gene, Peptidoglycan recognition protein 1 (Pglyrp1), in the mouse cornea. Here the expression of the Pglyrp1 transcript and the encoded protein, PGLYRP1, in the cornea was investigated. The role of PGLYRP1 in the cornea was further investigated using wild-type and Pglyrp1-deficient mice. This is the first report of this antimicrobial protein in the cornea.

Methods: PGLYRP1 was detected in the cornea and was further localized to the epithelium by immunohistology, confocal microscopy, immunoblotting, and real-time PCR. The role of PGLYRP1 in the cornea was investigated by comparing the response of wild-type and Pglyrp1(-/-) mice to corneal epithelial wounds and Pseudomonas aeruginosa-mediated corneal infections. The antibacterial effects of corneal PGLYRP1 were assayed by measuring bacterial growth in vitro, in the presence of wild-type corneal epithelial extracts, before and after antibody-mediated blocking of PGLYRP1.

Results: PGLYRP1 is expressed at high levels in the mouse corneal epithelium. PGLYRP1 was localized to the mouse corneal epithelium and the human corneal epithelium. The Pglyrp1(-/-) mouse shows delayed healing and poor clearing of bacterial keratitis; in vitro its epithelial protein extract shows reduced bacteriostatic activity compared with wild-type mice.

Conclusions: PGLYRP1 is a novel antimicrobial protein of the corneal epithelium and protects the ocular surface from bacterial infections.

Citing Articles

Meganuclease targeting HSV-1 protects against herpetic keratitis: Application to corneal transplants.

Chapellier B, Guindolet D, Pereira D, Galetto R, Sahel J, Labetoulle M Mol Ther Nucleic Acids. 2022; 30:511-521.

PMID: 36457698 PMC: 9682361. DOI: 10.1016/j.omtn.2022.11.006.

Mammals' humoral immune proteins and peptides targeting the bacterial envelope: from natural protection to therapeutic applications against multidrug-resistant Gram-negatives.

Escobar-Salom M, Torrens G, Jordana-Lluch E, Oliver A, Juan C Biol Rev Camb Philos Soc. 2022; 97(3):1005-1037.

PMID: 35043558 PMC: 9304279. DOI: 10.1111/brv.12830.

Perinatal granulopoiesis and risk of pediatric asthma.

Turturice B, Theorell J, Koenig M, Tussing-Humphreys L, Gold D, Litonjua A Elife. 2021; 10.

PMID: 33565964 PMC: 7889076. DOI: 10.7554/eLife.63745.

The Effect of Permethrin Resistance on Transcriptome Following Ingestion of Zika Virus Infected Blood.

Zhao L, Alto B, Shin D, Yu F Viruses. 2018; 10(9).

PMID: 30200481 PMC: 6165428. DOI: 10.3390/v10090470.

Toll-like receptor-associated keratitis and strategies for its management.

Kaur A, Kumar V, Singh S, Singh J, Upadhyay N, Datta S 3 Biotech. 2017; 5(5):611-619.

PMID: 28324534 PMC: 4569616. DOI: 10.1007/s13205-015-0280-y.

References

Dziarski R, Gupta D . Mammalian PGRPs: novel antibacterial proteins. Cell Microbiol. 2006; 8(7):1059-69. DOI: 10.1111/j.1462-5822.2006.00726.x. View

Cho J, Fraser I, Fukase K, Kusumoto S, Fujimoto Y, Stahl G . Human peptidoglycan recognition protein S is an effector of neutrophil-mediated innate immunity. Blood. 2005; 106(7):2551-8. PMC: 1895263. DOI: 10.1182/blood-2005-02-0530. View

Hanna C, BICKNELL D, OBrien J . Cell turnover in the adult human eye. Arch Ophthalmol. 1961; 65:695-8. DOI: 10.1001/archopht.1961.01840020697016. View

Liu C, Xu Z, Gupta D, Dziarski R . Peptidoglycan recognition proteins: a novel family of four human innate immunity pattern recognition molecules. J Biol Chem. 2001; 276(37):34686-94. DOI: 10.1074/jbc.M105566200. View

Lee E, Evans D, Fleiszig S . Role of Pseudomonas aeruginosa ExsA in penetration through corneal epithelium in a novel in vivo model. Invest Ophthalmol Vis Sci. 2003; 44(12):5220-7. DOI: 10.1167/iovs.03-0229. View

Gordon Y, Huang L, Romanowski E, Yates K, Proske R, McDermott A . Human cathelicidin (LL-37), a multifunctional peptide, is expressed by ocular surface epithelia and has potent antibacterial and antiviral activity. Curr Eye Res. 2005; 30(5):385-94. PMC: 1497871. DOI: 10.1080/02713680590934111. View

Gipson I . Distribution of mucins at the ocular surface. Exp Eye Res. 2004; 78(3):379-88. DOI: 10.1016/s0014-4835(03)00204-5. View

Guan R, Mariuzza R . Peptidoglycan recognition proteins of the innate immune system. Trends Microbiol. 2007; 15(3):127-34. DOI: 10.1016/j.tim.2007.01.006. View

Wang H, Gupta D, Li X, Dziarski R . Peptidoglycan recognition protein 2 (N-acetylmuramoyl-L-Ala amidase) is induced in keratinocytes by bacteria through the p38 kinase pathway. Infect Immun. 2005; 73(11):7216-25. PMC: 1273900. DOI: 10.1128/IAI.73.11.7216-7225.2005. View

10.

Dziarski R, Gupta D . Peptidoglycan recognition in innate immunity. J Endotoxin Res. 2005; 11(5):304-10. DOI: 10.1179/096805105X67256. View

11.

Salzman N, Underwood M, Bevins C . Paneth cells, defensins, and the commensal microbiota: a hypothesis on intimate interplay at the intestinal mucosa. Semin Immunol. 2007; 19(2):70-83. DOI: 10.1016/j.smim.2007.04.002. View

12.

Ayabe T, Satchell D, Wilson C, Parks W, Selsted M, Ouellette A . Secretion of microbicidal alpha-defensins by intestinal Paneth cells in response to bacteria. Nat Immunol. 2001; 1(2):113-8. DOI: 10.1038/77783. View

13.

Wu F, Lee S, Schumacher M, Jun A, Chakravarti S . Differential gene expression patterns of the developing and adult mouse cornea compared to the lens and tendon. Exp Eye Res. 2008; 87(3):214-25. PMC: 3043597. DOI: 10.1016/j.exer.2008.06.001. View

14.

Barthel L, Raymond P . Improved method for obtaining 3-microns cryosections for immunocytochemistry. J Histochem Cytochem. 1990; 38(9):1383-8. DOI: 10.1177/38.9.2201738. View

15.

Haynes R, Tighe P, Dua H . Antimicrobial defensin peptides of the human ocular surface. Br J Ophthalmol. 1999; 83(6):737-41. PMC: 1723065. DOI: 10.1136/bjo.83.6.737. View

16.

Huang L, Jean D, Proske R, Reins R, McDermott A . Ocular surface expression and in vitro activity of antimicrobial peptides. Curr Eye Res. 2007; 32(7-8):595-609. PMC: 2430515. DOI: 10.1080/02713680701446653. View

17.

Steiner H . Peptidoglycan recognition proteins: on and off switches for innate immunity. Immunol Rev. 2004; 198:83-96. DOI: 10.1111/j.0105-2896.2004.0120.x. View

18.

Vij N, Roberts L, Joyce S, Chakravarti S . Lumican regulates corneal inflammatory responses by modulating Fas-Fas ligand signaling. Invest Ophthalmol Vis Sci. 2004; 46(1):88-95. DOI: 10.1167/iovs.04-0833. View

19.

Medzhitov R, Janeway Jr C . Innate immune recognition: mechanisms and pathways. Immunol Rev. 2000; 173:89-97. DOI: 10.1034/j.1600-065x.2000.917309.x. View

20.

Neish A . The gut microflora and intestinal epithelial cells: a continuing dialogue. Microbes Infect. 2002; 4(3):309-17. DOI: 10.1016/s1286-4579(02)01543-5. View