Abstract
Gingival epithelium plays a pivotal role in protecting the underlying periodontium from the microbial colonization found in the gingival sulcus. Having an appropriate phenotype displayed by gingival epithelial cells is a critical host component required for protection against bacterial invasion into gingival tissues. In the present study, gingival epithelial homeostasis associated with the CXCL-8/IL-8 chemokine response was investigated in vitro to determine the mechanisms that gingival epithelial cells utilize for sensing gram-positive and gram-negative microorganisms. The findings of this study have demonstrated, by using Fusobacterium nucleatum, a heterogeneity of gingival epithelial cell response by Toll-like receptor (TLR) 2, a lipoprotein sensor. Notably, however, lipopolysaccharide (LPS), a major virulence factor of gram-negative bacteria, is not recognized by gingival epithelial cells unless the LPS is internalized into the cells. Activation of TLR4 in gingival epithelial cells occurs in the endosome, an intracellular event that requires a vesicular acidification to turn on TLR4 signaling, indicating their stringency for fine-tuning a local LPS response. This study has identified a unique LPS sensing mechanism of the oral epithelium to overcome a periodontal infection associated with LPS derived from gram-negative microbes that arises during dysbiosis.
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References
Abreu, M. T., Vora, P., Faure, E., Thomas, L. S., Arnold, E. T., & Arditi, M. (2001). Decreased expression of Toll-like receptor-4 and MD-2 correlates with intestinal epithelial cell protection against dysregulated proinflammatory gene expression in response to bacterial lipopolysaccharide. Journal of Immunology, 167(3), 1609–1616.
Attstrom, R., & Schroeder, H. E. (1979). Effect of experimental neutropenia on initial gingivitis in dogs. Scandinavian Journal of Dental Research, 87(1), 7–23.
Coats, S. R., Do, C. T., Karimi-Naser, L. M., Braham, P. H., & Darveau, R. P. (2007). Antagonistic lipopolysaccharides block E. coli lipopolysaccharide function at human TLR4 via interaction with the human MD-2 lipopolysaccharide binding site. Cellular Microbiology, 9(5), 1191–1202.
Darveau, R. P. (2010). Periodontitis: A polymicrobial disruption of host homeostasis. Nature Reviews. Microbiology, 8(7), 481–490.
Darveau, R. P., & Hancock, R. E. (1983). Procedure for isolation of bacterial lipopolysaccharides from both smooth and rough Pseudomonas aeruginosa and Salmonella typhimurium strains. Journal of Bacteriology, 155(2), 831–838.
Darveau, R. P., Belton, C. M., Reife, R. A., & Lamont, R. J. (1998). Local chemokine paralysis, a novel pathogenic mechanism for Porphyromonas gingivalis. Infection and Immunity, 66(4), 1660–1665.
Darveau, R. P., Pham, T. T., Lemley, K., Reife, R. A., Bainbridge, B. W., Coats, S. R., et al. (2004). Porphyromonas gingivalis lipopolysaccharide contains multiple lipid A species that functionally interact with both toll-like receptors 2 and 4. Infection and Immunity, 72(9), 5041–5051.
Dickson, M. A., Hahn, W. C., Ino, Y., Ronfard, V., Wu, J. Y., Weinberg, R. A., et al. (2000). Human keratinocytes that express hTERT and also bypass a p16(INK4a)-enforced mechanism that limits life span become immortal yet retain normal growth and differentiation characteristics. Molecular and Cellular Biology, 20(4), 1436–1447.
Ellis, T. N., & Kuehn, M. J. (2010). Virulence and immunomodulatory roles of bacterial outer membrane vesicles. Microbiology and Molecular Biology Reviews, 74(1), 81–94.
Eskan, M. A., Jotwani, R., Abe, T., Chmelar, J., Lim, J. H., Liang, S., et al. (2012). The leukocyte integrin antagonist Del-1 inhibits IL-17-mediated inflammatory bone loss. Nature Immunology, 13(5), 465–473.
Fitzgerald, J. E., & Kreutzer, D. L. (1995). Localization of interleukin-8 in human gingival tissues. Oral Microbiology and Immunology, 10(5), 297–303.
Gemmell, E., Walsh, L. J., Savage, N. W., & Seymour, G. J. (1994). Adhesion molecule expression in chronic inflammatory periodontal disease tissue. Journal of Periodontal Research, 29(1), 46–53.
Glew, M. D., Veith, P. D., Chen, D., Gorasia, D. G., Peng, B., & Reynolds, E. C. (2017). PorV is an outer membrane shuttle protein for the type IX secretion system. Scientific Reports, 7(1), 8790.
Greer, A., Irie, K., Hashim, A., Leroux, B. G., Chang, A. M., Curtis, M. A., et al. (2016). Site-specific neutrophil migration and CXCL2 expression in periodontal tissue. Journal of Dental Research, 95(8), 946–952.
Hagar, J. A., Powell, D. A., Aachoui, Y., Ernst, R. K., & Miao, E. A. (2013). Cytoplasmic LPS activates caspase-11: Implications in TLR4-independent endotoxic shock. Science, 341(6151), 1250–1253.
Hornef, M. W., Frisan, T., Vandewalle, A., Normark, S., & Richter-Dahlfors, A. (2002). Toll-like receptor 4 resides in the Golgi apparatus and colocalizes with internalized lipopolysaccharide in intestinal epithelial cells. The Journal of Experimental Medicine, 195(5), 559–570.
Hornef, M. W., Normark, B. H., Vandewalle, A., & Normark, S. (2003). Intracellular recognition of lipopolysaccharide by Toll-like receptor 4 in intestinal epithelial cells. The Journal of Experimental Medicine, 198(8), 1225–1235.
Husebye, H., Halaas, O., Stenmark, H., Tunheim, G., Sandanger, O., Bogen, B., et al. (2006). Endocytic pathways regulate Toll-like receptor 4 signaling and link innate and adaptive immunity. The EMBO Journal, 25(4), 683–692.
Jain, S., Coats, S. R., Chang, A. M., & Darveau, R. P. (2013). A novel class of lipoprotein lipase-sensitive molecules mediates Toll-like receptor 2 activation by Porphyromonas gingivalis. Infection and Immunity, 81(4), 1277–1286.
Johnson, L. S., Dunn, K. W., Pytowski, B., & McGraw, T. E. (1993). Endosome acidification and receptor trafficking: Bafilomycin A1 slows receptor externalization by a mechanism involving the receptor’s internalization motif. Molecular Biology of the Cell, 4(12), 1251–1266.
Kagan, J. C., Su, T., Horng, T., Chow, A., Akira, S., & Medzhitov, R. (2008). TRAM couples endocytosis of Toll-like receptor 4 to the induction of interferon-beta. Nature Immunology, 9(4), 361–368.
Krisanaprakornkit, S., Weinberg, A., Perez, C. N., & Dale, B. A. (1998). Expression of the peptide antibiotic human beta-defensin 1 in cultured gingival epithelial cells and gingival tissue. Infection and Immunity, 66(9), 4222–4228.
Melmed, G., Thomas, L. S., Lee, N., Tesfay, S. Y., Lukasek, K., Michelsen, K. S., et al. (2003). Human intestinal epithelial cells are broadly unresponsive to Toll-like receptor 2-dependent bacterial ligands: Implications for host-microbial interactions in the gut. Journal of Immunology, 170(3), 1406–1415.
Moffatt-Jauregui, C. E., Robinson, B., de Moya, A. V., Brockman, R. D., Roman, A. V., Cash, M. N., et al. (2013). Establishment and characterization of a telomerase immortalized human gingival epithelial cell line. Journal of Periodontal Research, 48(6), 713–721.
Moutsopoulos, N. M., Konkel, J., Sarmadi, M., Eskan, M. A., Wild, T., Dutzan, N., et al. (2014). Defective neutrophil recruitment in leukocyte adhesion deficiency type I disease causes local IL-17-driven inflammatory bone loss. Science Translational Medicine, 6(229), 229ra40.
Nakamura, H., Yoshimura, K., Jaffe, H. A., & Crystal, R. G. (1991). Interleukin-8 gene expression in human bronchial epithelial cells. The Journal of Biological Chemistry, 266(29), 19611–19617.
Ren, L., Leung, W. K., Darveau, R. P., & Jin, L. (2005). The expression profile of lipopolysaccharide-binding protein, membrane-bound CD14, and Toll-like receptors 2 and 4 in chronic periodontitis. Journal of Periodontology, 76(11), 1950–1959.
Schueller, K., Riva, A., Pfeiffer, S., Berry, D., & Somoza, V. (2017). Members of the oral microbiota are associated with IL-8 release by gingival epithelial cells in healthy individuals. Frontiers in Microbiology, 8, 416.
Sugiyama, A., Uehara, A., Iki, K., Matsushita, K., Nakamura, R., Ogawa, T., et al. (2002). Activation of human gingival epithelial cells by cell-surface components of black-pigmented bacteria: Augmentation of production of interleukin-8, granulocyte colony-stimulating factor and granulocyte-macrophage colony-stimulating factor and expression of intercellular adhesion molecule 1. Journal of Medical Microbiology, 51(1), 27–33.
Takeuchi, O., Hoshino, K., Kawai, T., Sanjo, H., Takada, H., Ogawa, T., et al. (1999). Differential roles of TLR2 and TLR4 in recognition of gram-negative and gram-positive bacterial cell wall components. Immunity, 11(4), 443–451.
To, T. T., Gumus, P., Nizam, N., Buduneli, N., & Darveau, R. P. (2016). Subgingival plaque in periodontal health antagonizes at toll-like receptor 4 and inhibits E-selectin expression on endothelial cells. Infection and Immunity, 84(1), 120–126.
Tonetti, M. S. (1997). Molecular factors associated with compartmentalization of gingival immune responses and transepithelial neutrophil migration. Journal of Periodontal Research, 32(1 Pt 2), 104–109.
Tonetti, M. S., Imboden, M. A., & Lang, N. P. (1998). Neutrophil migration into the gingival sulcus is associated with transepithelial gradients of interleukin-8 and ICAM-1. Journal of Periodontology, 69(10), 1139–1147.
Tsukamoto, Y., Usui, M., Yamamoto, G., Takagi, Y., Tachikawa, T., Yamamoto, M., et al. (2012). Role of the junctional epithelium in periodontal innate defense and homeostasis. Journal of Periodontal Research, 47(6), 750–757.
Ueta, M., Nochi, T., Jang, M. H., Park, E. J., Igarashi, O., Hino, A., et al. (2004). Intracellularly expressed TLR2s and TLR4s contribution to an immunosilent environment at the ocular mucosal epithelium. Journal of Immunology, 173(5), 3337–3347.
Uronen-Hansson, H., Allen, J., Osman, M., Squires, G., Klein, N., & Callard, R. E. (2004). Toll-like receptor 2 (TLR2) and TLR4 are present inside human dendritic cells, associated with microtubules and the Golgi apparatus but are not detectable on the cell surface: Integrity of microtubules is required for interleukin-12 production in response to internalized bacteria. Immunology, 111(2), 173–178.
Zenobia, C., Luo, X. L., Hashim, A., Abe, T., Jin, L., Chang, Y., et al. (2013). Commensal bacteria-dependent select expression of CXCL2 contributes to periodontal tissue homeostasis. Cellular Microbiology, 15(8), 1419–1426.
Acknowledgements
This study was supported by NIH NIDCR grant number RO1DE023453 awarded to Richard P. Darveau. Anandamahidol scholarship 2011 was awarded to Nutthapong Kantrong.
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Kantrong, N., To, T.T., Darveau, R.P. (2019). Gingival Epithelial Cell Recognition of Lipopolysaccharide. In: Belibasakis, G.N., Hajishengallis, G., Bostanci, N., Curtis, M.A. (eds) Oral Mucosal Immunity and Microbiome. Advances in Experimental Medicine and Biology, vol 1197. Springer, Cham. https://doi.org/10.1007/978-3-030-28524-1_5
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DOI: https://doi.org/10.1007/978-3-030-28524-1_5
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