Recognition of bacterial peptidoglycan by the innate immune system

Cellular and Molecular Life Sciences

Volumn 60, Issue 9, 2003, Pages 1793-1804

  Dziarski, R ^a  

^a INDIANA UNIVERSITY   (United States)

Author keywords

Bacterial cell wall; CD 14; Innate immunity; Muramyl peptides; Nod; Pattern recognition receptors; Peptidoglycan recognition proteins; Toll like receptor 2

Indexed keywords

AMIDASE; CD14 ANTIGEN; LYSOZYME; NUCLEOTIDE BINDING PROTEIN; PEPTIDOGLYCAN POLYSACCHARIDE; PROTEIN; TOLL LIKE RECEPTOR 2;

AMINO ACID COMPOSITION; BACTERIAL CELL WALL; CELL SHAPE; CELLULAR IMMUNITY; DROSOPHILA; GRAM NEGATIVE BACTERIUM; GRAM POSITIVE BACTERIUM; MOLECULAR RECOGNITION; NONHUMAN; OSMOTIC PRESSURE; PROTEIN ANALYSIS; PROTEIN CROSS LINKING; PROTEIN DOMAIN; PROTEIN FAMILY; REVIEW; STRUCTURAL HOMOLOGY; UPREGULATION;

ADAPTOR PROTEINS, SIGNAL TRANSDUCING; ANIMALS; ANTIGENS, CD14; BACTERIA; CARRIER PROTEINS; HUMANS; IMMUNE SYSTEM; IMMUNITY, NATURAL; MEMBRANE GLYCOPROTEINS; MOLECULAR STRUCTURE; NOD1 SIGNALING ADAPTOR PROTEIN; PEPTIDOGLYCAN; RECEPTORS, CELL SURFACE; TOLL-LIKE RECEPTOR 2; TOLL-LIKE RECEPTORS;

BACTERIA (MICROORGANISMS); EUKARYOTA; MAMMALIA; NEGIBACTERIA; POSIBACTERIA;

EID: 0141861083     PISSN: 1420682X     EISSN: None     Source Type: Journal    
DOI: 10.1007/s00018-003-3019-6     Document Type: Review

References (107)

1. Hoffmann J. A., Kafatos F. C., Janeway C. A. and Ezekowitz R. A. B. (1999) Phylogenetic perspectives in innate immunity. Science 284: 1313-1318
2. Aderem A. and Ulevitch R. J. (2000) Toll-like receptors in the induction of the innate immune responses. Nature 406: 782-787
3. Janeway C. and Medzhitov R. (2002) Innate immune recognition. Annu. Rev. Immunol. 20: 197-216
4. Schnare M., Barton G. M., Czopik Holt A., Takeda K., Akira S. and Medzhitov R. (2001) Toll-like receptors control activation of adaptive immune responses. Nat. Immunol. 2: 947-950
5. Hoffmann J. A. and Reichhart J.-M. (2002) Drosophila innate immunity: an evolutionary perspective. Nat. Immunol. 3: 121-126
6. Schleifer K. H. and Kandler O. (1972) Peptidoglycan types of bacterial cell walls and their taxonomic implications. Bacteriol. Rev. 36: 407-477
7. Doyle R. J. and Dziarski R. (2001) The bacterial cell: peptidoglycan. In: Molecular Medical Microbiology, pp. 137-153, Sussman M. (ed.), Academic Press, London
8. Rosenthal R. S. and Dziarski R. (1994) Isolation of peptidoglycan and soluble peptidoglycan fragments. Methods Enzymol. 235: 253-285
9. Barclay A. N., Brown M. H., Law S. K. A., McKnight A. J., Tomlinson M. G. and van der Merwe P. A. (1997) The Leukocyte Antigen Facts Book, Academic Press, San Diego
10. Kobe B. and Deisenhofer J. (1994) The leucine-rich repeat: a versatile binding motif. Trends Biochem. Sci. 19: 415-421
11. Wright S. D., Ramos R. A., Tobias P. S., Ulevitch R. J. and Mathison J. C. (1990) CD14, a receptor for complexes of lipopolysaccharide (LPS) and LPS binding protein. Science 249: 1431-1433
12. Weidemann B., Brade H., Rietschel E. T., Dziarski R., Bazil V., Kusumoto S. et al. (1994) Soluble peptidoglycan-induced monokine production can be blocked by anti-CD14 monoclonal antibodies and by lipid A partial structures. Infect. Immun. 62: 4709-4715
13. Pugin J., Heumann D., Tomasz A., Kravchenko V. V., Akamatsu Y., Nishijima M. et al. (1994) CD14 is a pattern recognition receptor. Immunity 1: 509-516
14. Gupta D., Kirkland T. N., Viriyakosol S. and Dziarski R. (1996) CD14 is a cell-activating receptor for bacterial peptidoglycan. J. Biol. Chem. 271: 23310-23316
15. Gupta D., Wang Q., Vinson C. and Dziarski R. (1999) Bacterial peptidoglycan induces CD 14-dependent activation of transcription factors CREB/ATF and AP-1. J. Biol. Chem. 274: 14012-14020
16. Weidemann B., Schletter J., Dziarski R., Kusumoto S., Stelter F., Rietschel E. T. et al. (1997) Specific binding of soluble peptidoglycan and muramyldipeptide to CD14 on human monocytes. Infect. Immun. 65: 858-864
17. Dziarski R., Tapping R. I. and Tobias P. (1998) Binding of bacterial peptidoglycan to CD14. J. Biol. Chem. 273: 8680-8690
18. Dziarski R., Ulmer A. J. and Gupta D. (2000) Interactions of bacterial lipopolysaccharide and peptidoglycan with mammalian CD14. In: Glycomicrobiology, pp. 145-186, Doyle R. J. (ed.), Kluwer Academic/Plenum Publishers, New York
19. Dziarski R, Ulmer A. J. and Gupta D. (2000) Interactions of CD14 with components of Gram-positive bacteria. Chem. Immunol. 74: 83-107
20. Frey E. A., Miller D. S., Jahr T. G., Sundan A., Bazil V., Espevik T. et al. (1992) Soluble CD14 participates in the response of cells to lipopolysaccharide. J. Exp. Med. 176: 1665-1671
21. Pugin J., Schurer-Maly C.-C., Leturq D., Moriarty A., Ulevitch R. J. and Tobias P. S. (1993) Lipopolysaccharide activation of human endothelial and epithelial cells is mediated by lipopolysaccharide-binding protein and soluble CD14. Proc. Natl. Acad. Sci. USA 90: 2744-2748
22. Jin Y., Gupta D. and Dziarski R. (1998) Endothelial and epithelial cells do not respond to complexes of peptidoglycan with soluble CD14, but are activated indirectly by peptidoglycan-induced tumor necrosis factor-α and interleukin-1 from monocytes. J. Infect. Dis. 177: 1629-1638
23. Dziarski R., Viriyakosol S., Kirkland T. N. and Gupta D. (2000) Soluble CD14 enhances membrane CD14-mediated responses to peptidoglycan: structural requirements differ from those for responses to lipopolysaccharide. Infect. Immun. 68: 5254-5260
24. Tobias P. S., Soldau K., Gegner J. A., Mintz D. and Ulevitch R. J. (1995) Lipopolysaccharide binding protein-mediated complexation of lipopolysaccharide with soluble CD14. J. Biol. Chem. 270: 10482-10488
25. Delude R. L., Savedra R., Zhao H., Thieringer R., Yamamoto S., Fenton M. J. et al. (1995) CD14 enhances cellular responses to endotoxin without imparting ligand-specific recognition. Proc. Natl. Acad. Sci. USA 92: 9288-9292
26. Haziot A., Ferrero E., Kontgen F., Hijiya N., Yamamoto S., Silver J. et al. (1996) Resistance to endotoxin shock and reduced dissemination of Gram-negative bacteria in CD14-deficient mice. Immunity 4: 407-414
27. Haziot A., Lin X. Y., Zhang F. and Goyert S. M. (1998) The induction of acute phase proteins by lipopolysaccharide uses a novel pathway that is CD14-independent. J. Immunol. 160: 2570-2572
28. Haziot A., Hijiya N., Schultz K., Zhang F., Gangloff S. C. and Goyert S. M. (1999) CD14 plays no major role in shock induced by Staphylococcus aureus but down-regulates TNF-α production. J. Immunol. 162: 4801-4805
29. Lemaitre B., Nickolas E., Michaut L., Reichhart J. M. and Hoffmann J. A. (1996) The dorsoventral regulatory gene cassette spatzle/Toll/cactus controls the potent antifungal response in Drosophila adults. Cell 86: 973-983
30. Hashimoto C., Hudson K. L. and Anderson K. V. (1988) The Toll gene in Drosophila, required for dorsal-ventral embryonic polarity, appears to encode transmembrane protein. Cell 52: 269-279
31. Medzhitov R. (2001) Toll-like receptors and innate immunity. Nat. Rev. Immunol. 1: 135-145
32. Medzhitov R., Preston-Hurlburt P. and Janeway C. A. (1997) A human homologue of the Drosophila Toll protein signals activation of adaptive immunity. Nature 388: 394-397
33. Rock F. L., Hardiman G., Timans C. J., Kastelein R. A. and Bazan J. F. (1998) A family of human receptors structurally related to Drosophila Toll. Proc. Natl. Acad. Sci. USA 95: 588-593
34. Yang R.-B., Mark M. R., Gray A., Huang A., Xie M. H., Zhang M. et al. (1998) Toll-like receptor-2 mediates lipopolysaccharide-induced cellular signaling. Nature 395: 284-288
35. Kirschning C. J., Wesche H., Ayres T. M. and Rothe M. (1998) Human Toll-like receptor 2 confers responsiveness to bacterial lipopolysaccharide. J. Exp. Med. 188: 2091-2097
36. Poltorak A., He V., Smirnova I., Liu M.-Y., Van Huffel C., Du X. et al. (1998) Defective LPS signaling in C3H/HeJ and C57BL/10ScCr mice: mutations in Tlr4 gene. Science 282: 2085-2088
37. Qureshi S. T., Lariviere L., Leveque G., Clermont S., Moore K. J., Gros P. et al. (1999) Endotoxin-tolerant mice have mutations in Toll-like receptor 4 (Tlr4). J. Exp. Med. 189: 615-625
38. Hirschfeld M., Ma Y., Weis J. H., Vogel S. N. and Weis J. J. (2000) Repurification of lipopolysaccharide eliminates signaling through both human and murine Toll-like receptor 2. J. Immunol. 165: 618-622
39. Dziarski R., Wang Q., Miyake K., Kirschning C. J. and Gupta D. (2001) MD-2 enables Toll-like receptor-2 (TLR2)-mediated responses to LPS and enhances TLR2-mediated responses to Gram-positive and Gram-negative bacteria and their cell wall components. J. Immunol. 166: 1938-1944
40. Shimazu R., Akashi S., Ogata H., Nagai Y., Fukudome K., Miyake K, et al. (1999) MD-2, a molecule that confers lipopolysaccharide responsiveness on Toll-like receptor 4. J. Exp. Med. 189: 1777-1782
41. da Silva Correia J., Soldau K., Christen U., Tobias P. S. and Ulevitch R. J. (2001) Lipopolysaccharide is in close proximity to each of the proteins in its membrane receptor complex. Transfer from CD14 to TLR4 and MD-2. J. Immunol. 276: 21129-21135
42. Schwandner R., Dziarski R., Wesche H., Rothe M. and Kirschning C. J. (1999) Peptidoglycan- and lipoteichoic acid-induced cell activation is mediated by Toll-like receptor 2. J. Biol. Chem. 274: 17406-17409
43. Yoshimura A., Lien E., Ingalls R. R., Tuomanen E., Dziarski R. and Golenbock D. (1999) Recognition of Gram-positive bacterial cell wall components by the innate immune system occurs via Toll-like receptor 2. J. Immunol. 163: 1-5
44. Takeuchi O., Hoshino K., Kawai T., Sanjo H., Takada H. and Ogawa T. (1999) Differential roles of TLR2 and TLR4 in recognition of Gram-negative and Gram-positive bacterial cell wall components. Immunity 11: 443-451
45. Underhill D. M, Ozinsky A., Hajjar A. M., Stevens A., Willson C. B., Bassetti M. et al. (1999) The Toll-like receptor 2 is recruited to macrophage phagosomes and discriminates between pathogens. Nature 401: 811-815
46. Ozinsky A., Underhill D. M., Fontenot J. D., Hajjar A. M., Smith K. D., Willson C. B. et al. (2000) The repertoire for pattern recognition of pathogens by the innate immune system is defined by cooperation between Toll-like receptors. Proc. Natl. Acad. Sci. USA 97: 13766-13771
47. Michelsen K. S., Aicher A., Mohaupt M., Hartung T., Dimmeler S., Kirschning C. J. et al. (2001) The role of Toll-like receptors (TLRs) in bacteria-induced maturation of murine dendritic cells (DCs). Peptidoglycan and lipoteichoic acid are inducers of DC maturation and require TLR2. J. Biol. Chem. 276: 25680-25686
48. Morath S., Stadelmaier A., Geyer A., Schmidt R. R. and Hartung T. (2002) Synthetic lipoteichoic acid from Staphylococcus aureus is a potent stimulus of cytokine release. J. Exp. Med. 195: 1635-1640
49. Brightbill H. D., Libraty D. H., Krutzik S. R., Yang R. B., Belisle J. T., Bleharski J. R. et al. (1999) Host defense mechanisms triggered by microbial lipoproteins through Toll-like receptors. Science 285: 732-736
50. Lien E., Sellati T. J., Yoshimura A., Flo T. H., Rawadi G. and Finberg R. W. (1999) Toll-like receptor 2 functions as a pattern recognition receptor for diverse bacterial products. J. Biol. Chem. 274: 33419-33425
51. Hirschfeld M., Kirschning C. J., Schwandner R., Wesche H., Weis J. H., Wooten R. M. et al. (1999) Inflammatory signaling by Borrelia burgdorferi lipoproteins is mediated by Toll-like receptor 2. J. Immunol. 163: 2382-2386
52. Means T. K., Wang S., Lien E., Yoshimura A., Golenbock D. T. and M. Fenton. (1999) Human Toll-like receptors mediate cellular activation by Mycobacterium tuberculosis. J. Immunol. 163: 3920-3927
53. Underhill D. M., Ozinsky A., Smith K. D. and Aderem A. (1999) Toll-like receptor-2 mediates mycobacteria-induced proinflammatory signaling in macrophages. Proc. Natl. Acad. Sci. USA 96: 14459-14463
54. Aliprantis A. O., Yang R.-B., Mark M. R., Suggett S., Devaux B., Radolf J. D. et al. (1999) Cell activation and apoptosis by bacterial lipoproteins through Toll-like receptor-2. Science 285: 736-739
55. Campos M. A. S., Almeida I. C., Takeuchi O., Akira S., Valente E. P., Procopio D. O. et al. (2001) Activation of Toll-like receptor-2 by glycosylphosphatidylinositol anchors from a protozoan. J. Immunol. 167: 416-423
56. Li M., Carpio D. F., Zheng Y., Bruzzo P., Singh V., Ouaaz F. et al. (2001) An essential role of the NF-κB/Toll-like receptor pathway in induction of inflammatory and tissue-repair gene expression by necrotic cells. J. Immunol. 166: 7128-7135
57. Takeuchi O., Kawai T., Muhlradt P. F., Morr M., Radolf J. D., Zychlinsky A. et al. (2001) Discrimination of bacterial lipoproteins by Toll-like receptor 6. Int. Immunol. 13: 933-940
58. Takeuchi O., Sato S., Horiuchi T., Hoshino K., Takeda K., Dong Z. et al. (2002) Role of Toll-like receptor 1 in mediating immune responses to microbial lipoproteins. J. Immunol. 169: 10-14
59. Iwaki D., Mitsuzawa H., Murakami S., Sano H., Konishi M., Akino T. et al. (2002) The extracellular Toll-like receptor 2 domain directly binds peptidoglycan derived from Staphylococcus aureus. J. Biol. Chem. 277: 24315-24320
60. 39 is critical for the recognition of Staphylococcus aureus peptidoglycan. J. Biol. Chem. 276: 41350-41356
61. Xu Z., Dziarski R., Wang Q., Swartz K., Sakamoto K. M. and Gupta D. (2001) Bacterial peptidoglycan-induced tnf-α transcription is mediated through the transcription factors Egr-1, Elk-1, and NF-κB. J. Immunol. 167: 6975-6982
62. Majcherczyk P. A., Langen H., Heumann D., Fountoulakis M., Glauser M. P. and Moreillon P. (1999) Digestion of Streptococcus pneumoniae cell walls with its major peptidoglycan hydrolase releases branched stem peptides carrying proinflammatory activity. J. Biol. Chem. 274: 12537-12543
63. Muzio M., Bosisio D., Polentarutti N., D'amico G., Stoppacciaro A., Mancinelli R. et al. (2000) Differential expression and regulation of Toll-like receptors (TLR) in human leukocytes; selective expression of TLR3 in dendritic cells. J. Immunol. 164: 5998-6004
64. Wang Q., Dziarski R., Kirschning C. J., Muzio M. and Gupta D. (2001) Micrococci and peptidoglycan activate TLR2 → MyD88→IRAK→ TRAF→NIK→IKK→NF-κB signal transduction pathway that induces transcription of interleukin-8. Infect. Immun. 69: 2270-2276
65. Arbibe L., Mira J. P., Teusch N., Kline L., Guha M., Mackman N. et al. (2000) Toll-like receptor 2-mediated NF-κB activation requires a Rac1-dependent pathway. Nat. Immunol. 1: 533-540
66. Akira S. (2003) Mammalian Toll-like receptors. Curr. Opin. Immunol. 15: 5-11
67. Heymer B., Seidl P. H. and Schleifer K. H. (1985) Immunochemistry and biological activity of peptidoglycan. In: Immunology of the Bacterial Cell Envelope, pp. 11-46, Stewart-Tull D. E. S. and Davis M. (eds), J. Wiley, New York
68. Kotani S., Watanabe Y., Shimono T., Narita T., Kato K., Stewart-Tull D. E. S. et al. (1975) Immunodajuvant activities of cell walls, their water-soluble fractions and peptidoglycan subunits, prepared from various Gram-positive bacteria, and of synthetic N-acetylmuramyl peptides. Z. Immun. Forsch. Exp. Klin. Immunol. 149 S: 302-319
69. Kang D., Liu G., Lundstrom A., Gelius E. and Steiner H. (1998) A peptidoglycan recognition protein in innate immunity conserved from insects to mammals. Proc. Natl. Acad. Sci. USA 95: 10078-10082
70. Werner T., Liu G., Kang D., Ekengren S., Steiner H. and Hultmark D. (2000) A family of peptidoglycan recognition proteins in the fruit fly Drosophila melanogaster. Proc. Natl. Acad. Sci. USA 97: 13772-13777
71. Liu C., Xu Z., Gupta D. and Dziarski R. (2001) Peptidoglycan recognition proteins: a novel family of four human innate immunity pattern recognition molecules. J. Biol. Chem. 276: 34686-34694
72. Yoshida H., Kinoshita K. and Ashida M. (1996) Purification of peptidoglycan recognition protein from hemolymph of the silkworm, Bombyx mori. J. Biol. Chem. 271: 13854-13860
73. Ashida M. and Brey P. T. (1997) Recent advances in research on the insect prophenoloxidase cascade. In: Molecular Mechanisms of Immune Responses in Insects, pp. 135-172, Brey P. T. and Hultmark D. (eds), Chapman and Hall, London
74. Ochiai M. and Ashida M. (1999) A pattern recognition protein for peptidoglycan. Cloning of the cDNA and the gene of the silkworm, Bombyx mori. J. Biol. Chem. 274: 11854-11858
75. Christophides G. K., Zdobnov E., Barillas-Mury C., Birney E., Blandin S., Blass C. et al. (2002) Immunity-related genes and gene families in Anopheles gambiae. Science 298: 159-165
76. Dimopoulos G., Christophides G. K., Meister S., Schultz J., White K. P., Barillas-Mury C. et al. (2002) Genome expression analysis of Anopheles gambiae: responses to injury, bacterial challenge, and malaria infection. Proc. Natl. Acad. Sci. USA 99: 8814-8819
77. Michel T., Reichhart J.-M., Hoffmann J. A. and Royet J. (2001) Drosophila Toll is activated by Gram-positive bacteria through a circulating peptidoglycan recognition protein. Nature 414: 756-759
78. Ligoxygakis P., Pelte N., Hoffmann J. A. and Reichhart J.-M. (2002) Activation of Drosophila Toll during fungal infection by a blood serine protease. Science 297: 114-116
79. Gottar M., Gobert V., Michel T., Belvin M., Duyk G. and Hoffmann J. A. (2002) The Drosophila immune response against Gram-negative bacteria is mediated by a peptidoglycan recognition protein. Nature 416: 640-644
80. Choe K.-M., Werner T., Stoven S., Hultmark D. and Anderson K. V. (2002) Requirement for a peptidoglycan recognition protein (PGRP) in Relish activation and antibacterial immune responses in Drosophila. Science 296: 359-362
81. Ramet M., Manfruelli P., Pearson A., Mathey-Prevot B. and Ezekowitz R. A. B. (2002) Functional genomic analysis of phagocytosis and identification of a Drosophila receptor for E. coli. Nature 416: 644-648
82. Takehana A., Katsuyama T., Yano T., Oshima Y., Takada H., Aigaki T. et al. (2002) 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. USA 99: 13705-13710
83. Rehman A., Taishi P., Fang J., Majde J. A. and Krueger J. M. (2000) The cloning of a rat peptidoglycan recognition protein (PGRP) and its induction in brain by sleep deprivation. Cytokine 13: 8-17
84. Tydell C. C., Yount N., Tran D., Yuan J. and Selsted M. E. (2002) Isolation, characterization and antimicrobial properties of bovine oligosaccharide-binding protein. J. Biol. Chem. 277: 19658-19664
85. Cheng X., Zhang X., Pflugrath J. W. and Studier E.W. (1994) The structure of bacteriophage T7 lysozyme, a zinc amidase and an inhibitor of T7 RNA polymerase. Proc. Natl. Acad. Sci. USA 91: 4034-4038
86. Mellroth P., Karlsson J. and Steiner H. (2003) A scavenger function for a Drosophila peptidoglycan recognition protein. J. Biol. Chem. 278: 7059-7064
87. Dziarski R., Platt K. A., Gelius E., Steiner H. and Gupta D. (2003) Defect in neutrophil killing and increased susceptibility to infection with nonpathogenic Gram-positive bacteria in peptidoglycan recognition protein-S (PGRP-S)-deficient mice. Blood 102: in press
88. Liu C., Gelius E., Liu G., Steiner H. and Dziarski R. (2000) Mammalian peptidoglycan recognition protein binds peptidoglycan with high affinity, is expressed in neutrophils, and inhibits bacterial growth. J. Biol. Chem. 275: 24490-24499
89. Tydell C. C. and Selsted M. E. (2002) Binding and precipitation of LPS by a peptidoglycan recognition protein. Keystone Symposium on Innate Immunity: Evolution and Link to Adaptive Immunity, p. 74, #339
90. Inohara N., Ogura Y. and Nunez G. (2002) Nods: a family of cytosolic proteins that regulate the host response to pathogens. Curr. Opin. Microbiol. 5: 76-80
91. Ogura Y., Inohara N., Benito A., Chen F. F., Yamaoka S. and Nunez G. (2001) Nod2, a Nod1/Apaf-1 family member that is restricted to monocytes and activates NF-κB. J. Biol. Chem. 276: 4812-4818
92. Inohara N., Koseki T., Lin J., del Peso L., Lucas P. C., Chen F. F. et al. (2000) An induced proximity model for NF-κB activation in the Nod1/RICK and RIP signaling pathways. J. Biol. Chem. 275: 27823-27831
93. Girardin S. E., Toumebize R., Mavris M., Page A. L., Li X., Stark G. R. et al. (2001) CARD4/Nod1 mediates NF-κB and JNK activation by invasive Shigella flexneri. EMBO Rep. 2: 736-742
94. Hugot J. P., Chamaillard M., Zoualio H., Lesage S., Cezard J. P., Belaiche J. et al. (2001) Association of NOD2 leucine-rich repeat variants with susceptibility to Crohn's disease. Nature 411: 599-603
95. Ogura Y., Bonen D. K., Inohara N., Nicolae D. L., Chen F. F., Ramos R. et al. (2001) A frameshift mutation in NOD2 associated with susceptibility to Crohn's disease. Nature 411: 603-606
96. Miceli-Richard C., Lesage S., Rybojad M., Prieur A. M., Manouvrier Hanu S., Hafner R. et al. (2001) CARD15 mutations in Blau syndrome. Nat. Genet. 29: 19-20
97. Inohara N., Ogura Y., Chen F. F., Muto A. and Nunez G. (2001) Human Nod1 confers responsiveness to bacterial lipopolysaccharide. J. Biol. Chem. 276: 2551-2554
98. Inohara N., Ogura Y., Fontalba A., Gutierrez O., Pons F., Crespo J. et al. (2003) Host recognition of bacterial muramyl dipeptide mediated through NOD2: implications for Crohn's disease. J. Biol. Chem. 278: 5509-5512
99. Girardin S. E., Boneca I. G., Viala J., Chamaillard M., Labigne A., Thomas G. et al. (2003) Nod2 is a general sensor of peptidoglycan through muramyl dipeptide (MDP) detection. J. Biol. Chem. 278: 8869-8872
100. Girardin S. E., Boneca I. G., Carneiro L. A. M., Antignac A., Jéhanno M., Viala J. et al. (2003) Nod1 detects specifically gram-negative bacteria through G1cNAc-MurNAc tripeptide, a peptidoglycan motif. Science, in press
101. Ellouz F., Adam. A., Ciorbaru R. and Lederer E. (1974) Minimal structural requirements for adjuvant activity of bacterial peptidoglycan derivatives. Biochem. Biophys. Res. Commun. 59: 1317-1325
102. Wolfert M. A., Murray T. F., Boons G.-J. and Moore J. N. (2002) The origin of the synergistic effect of muramyl dipeptide with endotoxin and peptidoglycan. J. Biol. Chem. 277: 39179-39186
103. Ribi E. E., Cantrell J. L., Von Eschen K. B. and Schwartzman S. M. (1979) Enhancement of endotoxin shock by N-acetyl-muramyl-L-alanyl-(L-seryl)-D-isoglutamine (muramyl dipeptide). Cancer Res. 39: 4756-4759
104. Galelli A. and Chedid L. (1986) Induction of colony-stimulating activity (CSA) by a synthetic muramyl peptide (MDP): synergism with LPS and activity in C3H/HeJ mice and in endotoxin-tolerized mice. J. Immunol. 137: 3211-3215
105. Takada H. and Galanos C. (1987) Enhancement of endotoxin lethality and generation of anaphylactoid reactions by lipopolysaccharide in muramyl-dipeptide-treated mice. Infect. Immun. 55: 409-413
106. + mobilization or protein kinase C activation. Cell. Immunol. 111: 10-27
107. Leulier F., Parquet C., Pili-Floury S., Ryu J.-H., Caroff M., Lee W.-J. et al (2003) The Drosophila immune system detects bacteria through specific peptidoglycan recognition. Nature Immunol. 4: 478-484