The innate immune system recognizes micro-organisms through a series of pattern recognition receptors that are highly conserved in evolution. Peptidoglycan (PGN) is a unique and essential component of the cell wall of virtually all bacteria, is not present in eukaryotes, and is an excellent target for the innate immune system. Indeed, higher eukaryotes, including mammals, have several PGN recognition molecules, including CD14, Toll-like receptor 2 (TLR2), nucleotide oligomerization domain (Nod)-containing proteins, a family of peptidoglycan recognition proteins (PGRPs), and PGN-lytic enzymes (lysozyme and amidase). These molecules induce host responses to micro-organisms, degrade PGN, or have direct antimicrobial effects.
Doyle RJ, Dziarski R.The bacterial cell: peptidoglycan. In: Sussman M. (ed) Molecular Medical Microbiology. London: Academic Press, 2001; 137—153.
2.
Janeway C. Medzhitov R.Innate immune recognition. Annu Rev Immunol2002; 20: 197—216.
3.
Wright SD, Ramos RA, Tobias PS, Ulevitch RJ, Mathison JCCD14, a receptor for complexes of lipopolysaccharide (LPS) and LPS binding protein. Science1990; 249: 1431—1433.
4.
Pugin J., Heumann D., Tomasz A. et al. CD14 is a pattern recognition receptor. Immunity1994; 1: 509—516.
5.
Weidemann B. , Brade H., Rietschel ET et al. Soluble peptidoglycan-induced monokine production can be blocked by anti-CD14 monoclonal antibodies and by lipid A partial structures. Infect Immun1994; 62: 4709—4715.
6.
Gupta D., Kirkland TN, Viriyakosol S., Dziarski R.CD14 is a cell-activating receptor for bacterial peptidoglycan. J Biol Chem1996; 271: 23310—23316.
7.
Weidemann B. , Schletter J., Dziarski R. et al. Specific binding of soluble peptidoglycan and muramyl dipeptide to CD14 on human monocytes. Infect Immun1997; 65: 858—864.
8.
Dziarski R., Tapping RI, Tobias P.Binding of bacterial peptidoglycan to CD14. J Biol Chem1998; 273: 8680—8690.
9.
Gupta D., Wang Q., Vinson C., Dziarski R.Bacterial peptidoglycan induces CD14-dependent activation of transcription factors CREB/ATF and AP-1. J Biol Chem1999 ; 274: 14012—14020.
10.
Schwandner R., Dziarski R., Wesche H., Rothe M., Kirschning CJPeptidoglycan- and lipoteichoic acid-induced cell activation is mediated by Toll-like receptor 2. J Biol Chem1999; 274: 17406—17409.
11.
Dziarski R.Recognition of bacterial peptidoglycan by the innate immune system. Cell Mol Life Sci2003 ; 60: 1793—1804.
12.
Yoshimura A. , Lien E., Ingalls RR, Tuomanen E., Dziarski R., Golenbock D.Recognition of Gram-positive bacterial cell wall components by the innate immune system occurs via Toll-like receptor 2. J Immunol1999; 163: 1—5.
13.
Takeuchi O. , Hoshino K., Kawai T., Sanjo H., Takada H., Ogawa T.Differential roles of TLR2 and TLR4 in recognition of Gram-negative and Gram-positive bacterial cell wall components. Immunity1999; 11: 443—451.
14.
Ozinsky A., Underhill DM, Fontenot JD et al. The repertoire for pattern recognition of pathogens by the innate immune system is defined by cooperation between Toll-like receptors. Proc Natl Acad Sci USA2000; 97: 13766—13771.
15.
Takeuchi O. , Kawai T., Muhlradt PF et al. Discrimination of bacterial lipoproteins by Toll-like receptor 6. Int Immunol2001; 13: 933—940.
16.
Takeuchi O. , Sato S., Horiuchi T. et al. Role of Toll-like receptor 1 in mediating immune responses to microbial lipoproteins. J Immunol2002; 169: 10—14.
17.
Iwaki D., Mitsuzawa H., Murakami S. et al. The extracellular Toll-like receptor 2 domain directly binds peptidoglycan derived from Staphylococcus aureus. J Biol Chem2002; 277: 24315—24320.
18.
Mitsuzawa H. , Wada I., Sano H. et al. Extracellular Toll-like receptor 2 region containing Ser40-Ile64 but not Cys30-Ser39 is critical for the recognition of Staphylococcus aureus peptidoglycan. J Biol Chem2001; 276: 41350—41356.
19.
Travassos LH , Girardin SE, Philpott DJ et al. Toll-like receptor 2-dependent bacterial sensing does not occur via peptidoglycan recognition. EMBO Report2004; 5: 1000—1006.
20.
Dziarski R. , Gupta D.Staphylococcus aureus peptidoglycan is a Toll-like receptor 2 activator: a reevaluation. Infect Immun2005; 73: 5212—5216.
21.
Inohara N., Ogura Y., Nunez G.Nods: a family of cytosolic proteins that regulate the host response to pathogens . Curr Opin Microbiol2002; 5: 76—80.
22.
Girardin SE , Boneca IG, Carneiro Lam et al. Nod1 detects a unique muropeptide from Gram-negative bacterial peptidoglycan. Science2003; 300: 1584—1587.
23.
Chamaillard M., Hashimoto M., Horie Y. et al. An essential role for NOD1 in host recognition of bacterial peptidoglycan containing diaminopimelic acid. Nat Immunol2003; 7: 702—707.
24.
Girardin SE , Travassos LH, Herve M. et al. Peptidoglycan molecular requirements allowing detection by Nod1 and Nod2. J Biol Chem2003; 278: 41702—41708.
25.
Inohara N., Ogura Y., Fontalba A. et al. Host recognition of bacterial muramyl dipeptide mediated through NOD2: implications for Crohn's disease. J Biol Chem2003; 278: 5509—5512.
26.
Girardin SE , Boneca IG, Viala J. et al. Nod2 is a general sensor of peptidoglycan through muramyl dipeptide (MDP) detection. J Biol Chem2003; 278: 8869—8872.
27.
Inohara N., Ogura Y., Chen FF, Muto A, Nunez G. Human Nod1 confers responsiveness to bacterial lipopolysaccharide. J Biol Chem2001; 276: 2551—2554.
28.
Viala J., Chaput C., Boneca IG et al. Nod1 responds to peptidoglycan delivered by the Helicobacter pylori cag pathogenicity island. Nat Immunol2004; 5: 1166—1174.
29.
Dziarski R., Platt KA, Gelius E., Steiner H., Gupta D.Defect in neutrophil killing and increased susceptibility to infection with non-pathogenic Gram-positive bacteria in peptidoglycan recognition protein-S-deficient mice. Blood2003; 102: 689—697.
30.
Yoshida H., Kinoshita K., Ashida M.Purification of peptidoglycan recognition protein from hemolymph of the silkworm, Bombyx mori. J Biol Chem1996; 271: 13854—13860.
31.
Kang D., Liu G., Lundstrom A., Gelius E., Steiner H.A peptidoglycan recognition protein in innate immunity conserved from insects to mammals. Proc Natl Acad Sci USA1998; 95: 10078—10082.
32.
Werner T., Liu G., Kang D., Ekengren S., Steiner H., Hultmark D.A family of peptidoglycan recognition proteins in the fruit fly Drosophila melanogaster. Proc Natl Acad Sci USA2000; 97: 13772—13777.
33.
Liu C., Xu Z., Gupta D., Dziarski R.Peptidoglycan recognition proteins: a novel family of four human innate immunity pattern recognition molecules. J Biol Chem2001; 276: 34686—34694.
Christophides GK, Zdobnov E., Barillas-Mury C. et al. Immunity-related genes and gene families in Anopheles gambiae. Science2002; 298: 159—165.
36.
Dimopoulos G., Christophides GK, Meister S. et al. Genome expression analysis of Anopheles gambiae: responses to injury, bacterial challenge, and malaria infection. Proc Natl Acad Sci USA2002; 99: 8814—8819.
37.
Takehana A. , Katsuyama T., Yano T. et al. Overexpression of a pattern-recognition receptor, peptidoglycan-recognition protein-LE, activates Imd/Relish-mediated antibacterial defense and the prophenoloxidase cascade in Drosophila larvae . Proc Natl Acad Sci USA2002; 99: 13705—13710.
38.
Takehana A. , Yano T., Mita S., Kotani A., Oshima Y., Kurata S.Peptidoglycan recognition protein (PGRP)-LE and PGRP-LC act synergistically in Drosophila immunity. EMBO J2004; 23: 4690—4700.
39.
Lee MH, Osaki T., Lee JY et al. Peptidoglycan recognition proteins involved in 1,3-β-D-glucan-dependent prophenoloxidase activation system of insect. J Biol Chem2004; 279: 3218—3227.
40.
Mellroth P. , Karlsson J., Steiner H.A scavenger function for a Drosophila peptidoglycan recognition protein. J Biol Chem2003; 278: 7059—7064.
41.
Kim M-S., Byun M., Oh B-H.Crystal structure of peptidoglycan recognition protein LB from Drosophila melanogaster. Nat Immunol2003; 4: 787—793.
42.
Gelius E., Persson C., Karlsson J., Steiner H.A mammalian peptidoglycan recognition protein with N-acetylmuramoyl-L-alanine amidase activity. Biochem Biophys Res Commun2003; 306: 988—994.
43.
Wang Z-M., Li X., Cocklin RR et al. Human peptidoglycan recognition protein-L is an N-acetylmuramoyl-L-alanine amidase. J Biol Chem2003; 278: 49044—49052.
44.
Chang CI, Pili-Floury S., Herve M. et al. A Drosophila pattern recognition receptor contains a peptidoglycan docking groove and unusual L,D-carboxypeptidase activity. PLoS Biol2004; 2: 1293—1302.
45.
Michel T., Reichhart J-M., Hoffmann JA, Royet J.Drosophila Toll is activated by Gram-positive bacteria through a circulating peptidoglycan recognition protein. Nature2001; 414: 756—759.
46.
Leulier F., Parquet C., Pili-Floury S. et al. The Drosophila immune system detects bacteria through specific peptidoglycan recognition. Nat Immunol2003 : 4: 478—484.
47.
Gobert V., Gottar M., Matskevich AA et al. Dual activation of the Drosophila Toll pathway by two pattern recognition receptors. Science2003; 302: 2126—2130.
48.
Pili-Floury S., Leulier F., Takahashi K. et al. In vivo RNA interference analysis reveals an unexpected role for GNBP1 in the defense against Gram-positive bacterial infection in Drosophila adults. J Biol Chem2004; 279: 12848—12853.
49.
Bischoff V. , Vignal C., Boneca IG, Michel T., Hoffmann JA, Royet J.Function of the Drosophila pattern-recognition receptor PGRP-SD in the detection of Gram-positive bacteria. Nat Immunol2004; 5: 1175-1180.
Choe K-M., Werner T., Stoven S., Hultmark D., Anderson KVRequirement for a peptidoglycan recognition protein (PGRP) in Relish activation and antibacterial immune responses in Drosophila. Science2002; 296: 359—362.
52.
Gottar M., Gobert V., Michel T., Belvin M., Duyk G., Hoffmann JAThe Drosophila immune response against Gram-negative bacteria is mediated by a peptidoglycan recognition protein. Nature2002; 416: 640—644.
53.
Ramet M., Manfruelli P., Pearson A., Mathey-Prevot B., Ezekowitz Rab.Functional genomic analysis of phagocytosis and identification of a Drosophila receptor for E. coli. Nature2002; 416: 644—648.
54.
Werner T., Borge-Renberg K., Mellroth P., Steiner H., Hultmark D.Functional diversity of the Drosophila PGRP-LC gene cluster in the response to lipopolysaccharide and peptidoglycan. J Biol Chem2003; 278: 26319—26322.
55.
Stenbak CR, Ryu JH, Leulier F. et al. Peptidoglycan molecular requirements allowing detection by the Drosophila immune deficiency pathway. J Immunol204; 173: 7339—7348.
56.
Liu C., Gelius E., Liu G., Steiner H., Dziarski R.Mammalian peptidoglycan recognition protein binds peptidoglycan with high affinity, is expressed in neutrophils, and inhibits bacterial growth. J Biol Chem2000; 275: 24490—24499.
57.
Tydell CC, Yount N., Tran D., Yuan J., Selsted M.Isolation, characterization, and antimicrobial properties of bovine oligosaccharide-binding protein. J Biol Chem2002; 277: 19658—19664.
58.
Mollner S., Braun V.Murein hydrolase (N-acetyl-muramoyl-L-alanine amidase) in human serum. Arch Microbiol1984; 140: 171—177.
59.
Vanderwinkel E., De Vlieghere M., De Pauw P. et al. Purification and characterization of N-acetylmuramoyl-L-alanine amidase from human serum. Biochim Biophys Acta1990; 1039: 331—338.
60.
Hoijer MA, Melief M-J., Keck W., Hazenberg MPPurification and characterization of N-acetylmuramoyl-L-alanine amidase from human plasma using monoclonal antibodies. Biochim Biophys Acta1996; 1289: 57—64.
61.
Zhang Y., van der Fits L., Voerman JS et al. Identification of serum N-acetylmuramoyl-L-alanine amidase as liver peptidoglycan recognition protein 2. Biochim Biophys Acta2005; 1752: 34—46.
62.
Wang H., Gupta D., Li X., Dziarski R.Peptidoglycan recognition protein 2 (N-acetylmuramoyl-L-alanine amidase) is induced in keratinocytes by bacteria through p38 kinase pathway. Infect Immun2005; 73: In press.
63.
Hoijer MA, Melief M-J., Debets R., Hazenberg MPInflammatory properties of peptidoglycan are decreased after degradation with human N-acetylmuramoyl-L-alanine amidase. Eur Cytokine Netw1997; 8: 375—382.
Ganz T., Gabayan V., Liao H-I. et al. Increased inflammation in lysozyme M-deficient mice in response to Micrococcus luteus and its peptidoglycan. Blood2002; 101: 2388—2392.
