In bacterial infection, Nucleotide-binding Oligomerization Domain (NOD) 1 and NOD2 induce innate immune responses by recognizing fragments of the bacterial component peptidoglycan (PGN). To determine the roles of these receptors in detection of periodontal pathogens, we stimulated human embryonic kidney cells expressing NOD1 or NOD2 with heat-killed Porphyromonas gingivalis, Aggregatibacter actinomycetemcomitans, and Fusobacterium nucleatum or their soluble PGNs (sPGNs). All bacteria and their sPGNs could stimulate activation of NF-κB. However, there were differences in NOD1- and NOD2-stimulatory activities among the species of bacteria. P. gingivalis showed weaker NOD1- and NOD2-stimulatory activities than did other bacteria. These differences in activities were confirmed by production of interleukin-8 from oral epithelial cells stimulated with sPGNs. These findings indicate that both NOD1 and NOD2 might be involved in the recognition of periodontal pathogens, and that the weak NOD-stimulatory property of P. gingivalis might be helpful for survival in the periodontal pocket.
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References
1.
Antignac A, Rousselle JC, Namane A, Labigne A, Taha MK, Boneca IG -2003-. Detailed structural analysis of the peptidoglycan of the human pathogen Neisseria meningitidis. J Biol Chem278:31521–31528.
2.
Barnard MR, Holt SC -1985-. Isolation and characterization of the peptidoglycans from selected Gram-positive and Gram-negative periodontal pathogens. Can J Microbiol31:154–160.
3.
Chamaillard M, Hashimoto M, Horie Y, Masumoto J, Qiu S, Saab L, et al. -2003-. An essential role for NOD1 in host recognition of bacterial peptidoglycan containing diaminopimelic acid. Nat Immunol4:702–707.
4.
Darveau RP, Belton CM, Reife RA, Lamont RJ -1998-. Local chemokine paralysis, a novel pathogenic mechanism for Porphyromonas gingivalis. Infect Immun66:1660–1665.
5.
de Jonge BL, Chang YS, Gage D, Tomasz A -1992-. Peptidoglycan composition of a highly methicillin-resistant Staphylococcus aureus strain. The role of penicillin binding protein 2A. J Biol Chem267:11248–11254.
6.
Girardin SE, Boneca IG, Carneiro LA, Antignac A, Jehanno M, Viala J, et al. -2003a-. Nod1 detects a unique muropeptide from Gram-negative bacterial peptidoglycan. Science300:1584–1587.
7.
Girardin SE, Boneca IG, Viala J, Chamaillard M, Labigne A, Thomas G, et al. -2003b-. Nod2 is a general sensor of peptidoglycan through muramyl dipeptide -MDP- detection. J Biol Chem278:8869–8872.
8.
Girardin SE, Travassos LH, Hervé M, Blanot D, Boneca IG, Philpott DJ, et al. -2003c-. Peptidoglycan molecular requirements allowing detection by Nod1 and Nod2. J Biol Chem278:41702–41708.
9.
Glauner B, Höltje JV, Schwarz U -1988-. The composition of the murein of Escherichia coli. J Biol Chem263:10088–10095.
10.
Grenier D, Mayrand D -1987-. Selected characteristics of pathogenic and non-pathogenic strains of Bacteroides gingivalis. J Clin Microbiol25:738–740.
11.
Han YW, Shi W, Huang GT, Kinder Haake S, Park NH, Kuramitsu H, et al. -2000-. Interactions between periodontal bacteria and human oral epithelial cells: Fusobacterium nucleatum adheres to and invades epithelial cells. Infect Immun68:3140–3146.
12.
Jandik KA, Belanger M, Low SL, Dorn BR, Yang MC, Progulske-Fox A -2008-. Invasive differences among Porphyromonas gingivalis strains from healthy and diseased periodontal sites. J Periodontal Res43:524–530.
13.
Kaneko T, Goldman WE, Mellroth P, Steiner H, Fukase K, Kusumoto S, et al. -2004-. Monomeric and polymeric Gram-negative peptidoglycan but not purified LPS stimulate the Drosophila IMD pathway. Immunity20:637–649.
14.
Kaneko T, Golenbock D, Silverman N -2005-. Peptidoglycan recognition by the Drosophila Imd pathway. J Endotoxin Res11:383–389.
15.
Kim YG, Park JH, Shaw MH, Franchi L, Inohara N, Núñez G -2008-. The cytosolic sensors Nod1 and Nod2 are critical for bacterial recognition and host defense after exposure to Toll-like receptor ligands. Immunity28:246–257.
16.
Kobayashi KS, Chamaillard M, Ogura Y, Henegariu O, Inohara N, Núñez G, et al. -2005-. Nod2-dependent regulation of innate and adaptive immunity in the intestinal tract. Science307:731–734.
17.
Lamont RJ, Chan A, Belton CM, Izutsu KT, Vasel D, Weinberg A -1995-. Porphyromonas gingivalis invasion of gingival epithelial cells. Infect Immun63:3878–3885.
18.
Magalhães JG, Philpott DJ, Nahori MA, Jehanno M, Fritz J, Le Bourhis L, et al. -2005-. Murine Nod1 but not its human orthologue mediates innate immune detection of tracheal cytotoxin. EMBO Rep6:1201–1207.
19.
Meyer DH, Sreenivasan PK, Fives-Taylor PM -1991-. Evidence for invasion of a human oral cell line by Actinobacillus actinomycetemcomitans. Infect Immun59:2719–2726.
20.
Neiders ME, Chen PB, Suido H, Reynolds HS, Zambon JJ, Shlossman M, et al. -1989-. Heterogeneity of virulence among strains of Bacteroides gingivalis. J Periodontal Res24:192–198.
21.
Nishihara T, Koseki T -2004-. Microbial etiology of periodontitis. Periodontol 200036:14–26.
22.
Ogawa T -1993-. Chemical structure of lipid A from Porphyromonas -Bacteroides- gingivalis lipopolysaccharide. FEBS Lett332:197–201.
23.
Schleifer KH, Kandler O -1972-. Peptidoglycan types of bacterial cell walls and their taxonomic implications. Bacteriol Rev36:407–477.
24.
Slots J, Reynolds HS, Genco RJ -1980-. Actinobacillus actinomycetemcomitans in human periodontal disease: a cross-sectional microbiological investigation. Infect Immun29:1013–1020.
25.
Socransky SS, Haffajee AD, Cugini MA, Smith C, Kent RL Jr -1998-. Microbial complexes in subgingival plaque. J Clin Periodontol25:134–144.
26.
Stewart-Tull DE -1980-. The immunological activities of bacterial peptidoglycans. Annu Rev Microbiol34:311–340.
27.
Sugawara Y, Uehara A, Fujimoto Y, Kusumoto S, Fukase K, Shibata K, et al. -2006-. Toll-like receptors, NOD1, and NOD2 in oral epithelial cells. J Dent Res85:524–529.
28.
Vasstrand EN, Hofstad T, Endresen C, Jensen HB -1979-. Demonstration of lanthionine as a natural constituent of the peptidoglycan of Fusobacterium nucleatum. Infect Immun25:775–780.
29.
Viala J, Chaput C, Boneca IG, Cardona A, Girardin SE, Moran AP, et al. -2004-. Nod1 responds to peptidoglycan delivered by the Helicobacter pylori cag pathogenicity island. Nat Immunol5:1166–1174.
30.
Yoshimura A, Lien E, Ingalls RR, Tuomanen E, Dziarski R, Golenbock D -1999-. Cutting edge: recognition of Gram-positive bacterial cell wall components by the innate immune system occurs via Toll-like receptor 2. J Immunol163:1–5.
31.
Yoshimura A, Kaneko T, Kato Y, Golenbock DT, Hara Y -2002-. Lipopolysaccharides from periodontopathic bacteria Porphyromonas gingivalis and Capnocytophaga ochracea are antagonists for human toll-like receptor 4. Infect Immun70:218–225.
