Oral Biofilms from Symbiotic to Pathogenic Interactions and Associated Disease -Connection of Periodontitis and Rheumatic Arthritis by Peptidylarginine Deiminase

Katja Kriebel, Cathleen Hieke, Brigitte Müller-Hilke, Masanobu Nakata, Bernd Kreikemeyer, Katja Kriebel, Cathleen Hieke, Brigitte Müller-Hilke, Masanobu Nakata, Bernd Kreikemeyer

Abstract

A wide range of bacterial species are harbored in the oral cavity, with the resulting complex network of interactions between the microbiome and host contributing to physiological as well as pathological conditions at both local and systemic levels. Bacterial communities inhabit the oral cavity as primary niches in a symbiotic manner and form dental biofilm in a stepwise process. However, excessive formation of biofilm in combination with a corresponding deregulated immune response leads to intra-oral diseases, such as dental caries, gingivitis, and periodontitis. Moreover, oral commensal bacteria, which are classified as so-called "pathobionts" according to a now widely accepted terminology, were recently shown to be present in extra-oral lesions with distinct bacterial species found to be involved in the onset of various pathophysiological conditions, including cancer, atherosclerosis, chronic infective endocarditis, and rheumatoid arthritis. The present review focuses on oral pathobionts as commensal and healthy members of oral biofilms that can turn into initiators of disease. We will shed light on the processes involved in dental biofilm formation and also provide an overview of the interactions of P. gingivalis, as one of the most prominent oral pathobionts, with host cells, including epithelial cells, phagocytes, and dental stem cells present in dental tissues. Notably, a previously unknown interaction of P. gingivalis bacteria with human stem cells that has impact on human immune response is discussed. In addition to this very specific interaction, the present review summarizes current knowledge regarding the immunomodulatory effect of P. gingivalis and other oral pathobionts, members of the oral microbiome, that pave the way for systemic and chronic diseases, thereby showing a link between periodontitis and rheumatoid arthritis.

Keywords: P. gingivalis; oral biofilm; peptidylarginine deiminase; periodontitis; rheumatic arthritis.

Figures

FIGURE 1
FIGURE 1
Brief overview of current concepts regarding onset of periodontitis and rheumatic arthritis, and deduced causal relationships between both diseases. After establishing a subgingival biofilm, oral pathobionts, including Porphyromonas gingivalis, induce periodontitis as a chronic disease, which is attributable to host-pathobiont interactions and deleterious host immune responses in periodontal tissues. Dysregulated citrullination caused by the pathobiont Porphyromonas gingivalis has been suspected to be a causative factor for onset of rheumatic arthritis. Parts of this figure were taken from freely available web resources: https://www.chirurgie-portal.de/innere-medizin/rheuma.html; www.rcsb.org/pdb/ngl/ngl.do?pdbid=5AK7 (Rosenstein and Hildebrand, 2015; Montgomery et al., 2016).
FIGURE 2
FIGURE 2
Development of gingivitis and periodontitis. Following dental plaque accumulation, neutrophils dominate the host immune response, accompanied by progression of an early or stable gingivitis lesion, along with increased infiltration of macrophages and T cells. The gingivitis lesion develops into a periodontitis lesion, which is characterized by formation of a pathogenic periodontal pocket and destruction of periodontal tissues. Infiltrated lymphocytes are dominated by B and plasma cells.

References

    1. Aas J. A., Paster B. J., Stokes L. N., Olsen I., Dewhirst F. E. (2005). Defining the normal bacterial flora of the oral cavity. J. Clin. Microbiol. 43 5721–5732. 10.1128/JCM.43.11.5721-5732.2005
    1. Abdullah S. N., Farmer E. A., Spargo L., Logan R., Gully N. (2013). Porphyromonas gingivalis peptidylarginine deiminase substrate specificity. Anaerobe 23 102–108. 10.1016/j.anaerobe.2013.07.001
    1. Aberdam D., Candi E., Knight R. A., Melino G. (2008). miRNAs, ‘stemness’ and skin. Trends Biochem. Sci. 33 583–591. 10.1016/j.tibs.2008.09.002
    1. AlJehani Y. A. (2014). Risk factors of periodontal disease: review of the literature. Int. J. Dent. 2014:182513. 10.1155/2014/182513
    1. Al-Katma M. K., Bissada N. F., Bordeaux J. M., Sue J., Askari A. D. (2007). Control of periodontal infection reduces the severity of active rheumatoid arthritis. J. Clin. Rheumatol. 13 134–137. 10.1097/RHU.0b013e3180690616
    1. Arita K., Hashimoto H., Shimizu T., Nakashima K., Yamada M., Sato M. (2004). Structural basis for Ca2+-induced activation of human PAD4. Nat. Struct. Mol. Biol. 11 777–783. 10.1038/nsmb799
    1. Barry F. P., Murphy J. (2004). Mesenchymal stem cells: clinical applications and biological characterization. Int. J. Biochem. Cell Biol. 36 568–584. 10.1016/j.biocel.2003.11.001
    1. Bartold P. M., Marino V., Cantley M., Haynes D. R. (2010). Effect of Porphyromonas gingivalis-induced inflammation on the development of rheumatoid arthritis. J. Clin. Periodontol. 37 405–411. 10.1111/j.1600-051X.2010.01552.x
    1. Benakanakere M. R., Li Q., Eskan M. A., Singh A. V., Zhao J., Galicia J. C., et al. (2009). Modulation of TLR2 protein expression by miR-105 in human oral keratinocytes. J. Biol. Chem. 284 23107–23115. 10.1074/jbc.M109.013862
    1. Berezow A. B., Darveau R. P. (2011). Microbial shift and periodontitis. Periodontol. 2000 55 36–47. 10.1111/j.1600-0757.2010.00350.x
    1. Bicker K. L., Thompson P. R. (2013). The protein arginine deiminases: structure, function, inhibition, and disease. Biopolymers 99 155–163. 10.1002/bip.22127
    1. Biedermann A., Kriebel K., Kreikemeyer B., Lang H. (2014). Interactions of anaerobic bacteria with dental stem cells: an in vitro study. PLOS ONE 9:e110616. 10.1371/journal.pone.0110616
    1. Bielecka E., Scavenius C., Kantyka T., Jusko M., Mizgalska D., Szmigielski B., et al. (2014). Peptidyl arginine deiminase from Porphyromonas gingivalis abolishes anaphylatoxin C5a activity. J. Biol. Chem. 289 32481–32487. 10.1074/jbc.C114.617142
    1. Brown S. A., Whiteley M. (2007). A novel exclusion mechanism for carbon resource partitioning in Aggregatibacter actinomycetemcomitans. J. Bacteriol. 189 6407–6414. 10.1128/JB.00554-07
    1. Brunner J., Scheres N., El Idrissi N. B., Deng D. M., Laine M. L., van Winkelhoff A. J., et al. (2010). The capsule of Porphyromonas gingivalis reduces the immune response of human gingival fibroblasts. BMC Microbiol. 10:5. 10.1186/1471-2180-10-5
    1. Carvalho-Filho P. C., Gomes-Filho I. S., Meyer R., Olczak T., Xavier M. T., Trindade S. C. (2016). Role of Porphyromonas gingivalis HmuY in immunopathogenesis of chronic periodontitis. Mediators Inflamm. 2016:7465852. 10.1155/2016/7465852
    1. Castro S. A., Collighan R., Lambert P. A., Dias I. H. K., Chauhan P., Bland C. E., et al. (2017). Porphyromonas gingivalis gingipains cause defective macrophage migration towards apoptotic cells and inhibit phagocytosis of primary apoptotic neutrophils. Cell Death Dis. 8:e2644. 10.1038/cddis.2016.481
    1. Catrina A. I., Svensson C. I., Malmstrom V., Schett G., Klareskog L. (2017). Mechanisms leading from systemic autoimmunity to joint-specific disease in rheumatoid arthritis. Nat. Rev. Rheumatol. 13 79–86. 10.1038/nrrheum.2016.200
    1. Chatzivasileiou K., Kriebel K., Steinhoff G., Kreikemeyer B., Lang H. (2015). Do oral bacteria alter the regenerative potential of stem cells? A concise review. J. Cell Mol. Med. 19 2067–2074. 10.1111/jcmm.12613
    1. Chatzivasileiou K., Lux C. A., Steinhoff G., Lang H. (2013). Dental follicle progenitor cells responses to Porphyromonas gingivalis LPS. J. Cell Mol. Med. 17 766–773. 10.1111/jcmm.12058
    1. Cortelli J. R., Aquino D. R., Cortelli S. C., Franco G. C. N., Fernandes C. B., Roman-Torres C. V. G., et al. (2008). Detection of periodontal pathogens in oral mucous membranes of edentulous individuals. J. Periodontol. 79 1962–1965. 10.1902/jop.2008.080092
    1. Damgaard C., Kantarci A., Holmstrup P., Hasturk H., Nielsen C. H., van Dyke T. E. (2016). Porphyromonas gingivalis-induced production of reactive oxygen species, tumor necrosis factor-α, interleukin-6 CXCL8 and CCL2 by neutrophils from localized aggressive periodontitis and healthy donors: modulating actions of red blood cells and resolvin E1. J. Periodontal Res. 52 246–254. 10.1111/jre.12388
    1. Darrah E., Giles J. T., Ols M. L., Bull H. G., Andrade F., Rosen A. (2013). Erosive rheumatoid arthritis is associated with antibodies that activate PAD4 by increasing calcium sensitivity. Sci. Transl. Med. 5:186ra165. 10.1126/scitranslmed.3005370
    1. de Pablo P., Chapple I. L., Buckley C. D., Dietrich T. (2009). Periodontitis in systemic rheumatic diseases. Nat. Rev. Rheumatol. 5 218–224. 10.1038/nrrheum.2009.28
    1. Deshpande R., Khan M., Genco C. (1998). Invasion of aortic and heart endothelial cells by Porphyromonas gingivalis. Infect. Immun. 66 5337–5343.
    1. Desta T., Graves D. T. (2007). Fibroblast apoptosis induced by Porphyromonas gingivalis is stimulated by a gingipain and caspase-independent pathway that involves apoptosis-inducing factor. Cell. Microbiol. 9 2667–2675. 10.1111/j.1462-5822.2007.00987.x
    1. Dewhirst F. E., Chen T., Izard J., Paster B. J., Tanner A. C. R., Yu W. H., et al. (2010). The human oral microbiome. J. Bacteriol 192 5002–5017. 10.1128/JB.00542-10
    1. Dogan S., Gunzer F., Guenay H., Hillmann G., Geurtsen W. (2000). Infection of primary human gingival fibroblasts by Porphyromonas gingivalis and Prevotella intermedia. Clin. Oral Investig. 4 35–41. 10.1007/s007840050111
    1. Dorn B., Burks J., Seifert K., Progulske-Fox A. (2000). Invasion of endothelial and epithelial cells by strains of Porphyromonas gingivalis. FEMS Microbiol. Lett. 187 139–144. 10.1111/j.1574-6968.2000.tb09150.x
    1. Duncan M. J., Nakao S., Skobe Z., Xie H. (1993). Interactions of Porphyromonas gingivalis with epithelial cells. Infect. Immun. 61 2260–2265.
    1. Duran-Pinedo A. E., Frias-Lopez J. (2015). Beyond microbial community composition: functional activities of the oral microbiome in health and disease. Microbes Infect. 17 505–516. 10.1016/j.micinf.2015.03.014
    1. Dutzan N., Abusleme L., Bridgeman H., Greenwell-Wild T., Zangerle-Murray T., Fife M. E., et al. (2017). On-going mechanical damage from mastication drives homeostatic Th17 cell responses at the oral barrier. Immunity 46 133–147. 10.1016/j.immuni.2016.12.010
    1. Eriksson K., Nise L., Kats A., Luttropp E., Catrina A. I., Askling J., et al. (2016). Prevalence of periodontitis in patients with established rheumatoid arthritis: a swedish population based case-control study. PLOS ONE 11:e0155956. 10.1371/journal.pone.0155956
    1. 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. Nat. Immunol. 13 465–473. 10.1038/ni.2260
    1. Feng Z., Weinberg A. (2006). Role of bacteria in health and disease of periodontal tissues. Periodontol. 2000 40 50–76. 10.1111/j.1600-0757.2005.00148.x
    1. Gaffen S. L., Herzberg M. C., Taubman M. A., van Dyke T. E. (2014). Recent advances in host defense mechanisms/therapies against oral infectious diseases and consequences for systemic disease. Adv. Dent. Res. 26 30–37. 10.1177/0022034514525778
    1. Gamonal J., Sanz M., O’Connor A., Acevedo A., Suarez I., Sanz A., et al. (2003). Delayed neutrophil apoptosis in chronic periodontitis patients. J. Clin. Periodontol. 30 616–623. 10.1034/j.1600-051X.2003.00350.x
    1. Gonzales J. R. (2015). T- and B-cell subsets in periodontitis. Periodontol. 2000 69 181–200. 10.1111/prd.12090
    1. Graves D. (2008). Cytokines that promote periodontal tissue destruction. J. Periodontol. 79 1585–1591. 10.1902/jop.2008.080183
    1. Gronthos S., Mankani M., Brahim J., Robey P., Shi S. (2000). Postnatal human dental pulp stem cells (DPSCs) in vitro and in vivo. Proc. Natl. Acad. Sci. U.S.A. 97 13625–13630. 10.1073/pnas.240309797
    1. Haffajee A. D., Socransky S. S., Patel M. R., Song X. (2008). Microbial complexes in supragingival plaque. Oral Microbiol. Immunol. 23 196–205. 10.1111/j.1399-302X.2007.00411.x
    1. Hajishengallis G. (2015). Periodontitis: from microbial immune subversion to systemic inflammation. Nat. Rev. Immunol. 15 30–44. 10.1038/nri3785
    1. Hajishengallis G., Lamont R. J. (2012). Beyond the red complex and into more complexity: the polymicrobial synergy and dysbiosis (PSD) model of periodontal disease etiology. Mol. Oral Microbiol. 27 409–419. 10.1111/j.2041-1014.2012.00663.x
    1. Hajishengallis G., Wang M., Bagby G. J., Nelson S. (2008). Importance of TLR2 in early innate immune response to acute pulmonary infection with Porphyromonas gingivalis in mice. J. Immunol. 181 4141–4149. 10.4049/jimmunol.181.6.4141
    1. Harre U., Georgess D., Bang H., Bozec A., Axmann R., Ossipova E., et al. (2012). Induction of osteoclastogenesis and bone loss by human autoantibodies against citrullinated vimentin. J. Clin. Invest. 122 1791–1802. 10.1172/JCI60975
    1. He J., Li Y., Cao Y., Xue J., Zhou X. (2015). The oral microbiome diversity and its relation to human diseases. Folia Microbiol. 60 69–80. 10.1007/s12223-014-0342-2
    1. Heaton B., Dietrich T. (2012). Causal theory and the etiology of periodontal diseases. Periodontol. 2000 58 26–36. 10.1111/j.1600-0757.2011.00414.x
    1. Heller D., Helmerhorst E. J., Oppenheim F. G. (2017). Saliva and serum protein exchange at the tooth enamel surface. J. Dent. Res. 96 437–443. 10.1177/0022034516680771
    1. Hieke C., Kriebel K., Engelmann R., Müller-Hilke B., Lang H., Kreikemeyer B. (2016). Human dental stem cells suppress PMN activity after infection with the periodontopathogens Prevotella intermedia and Tannerella forsythia. Sci. Rep. 6:39096. 10.1038/srep39096
    1. Hooper L. V., Littman D. R., Macpherson A. J. (2012). Interactions between the microbiota and the immune system. Science 336 1268–1273. 10.1126/science.1223490
    1. How K. Y., Song K. P., Chan K. G. (2016). Porphyromonas gingivalis: an overview of periodontopathic pathogen below the gum line. Front. Microbiol. 7:53 10.3389/fmicb.2016.00053
    1. Irshad M., van der Reijden W. A., Crielaard W., Laine M. L. (2012). In vitro invasion and survival of Porphyromonas gingivalis in gingival fibroblasts; role of the capsule. Arch. Immunol. Ther. Exp. 60 469–476. 10.1007/s00005-012-0196-8
    1. Ishida K., Kobayashi T., Ito S., Komatsu Y., Yokoyama T., Okada M., et al. (2012). Interleukin-6 gene promoter methylation in rheumatoid arthritis and chronic periodontitis. J. Periodontol. 83 917–925. 10.1902/jop.2011.110356
    1. Jenkinson H. F. (1994). Cell surface protein receptors in oral streptococci. FEMS Microbiol. Lett. 121 133–140. 10.1111/j.1574-6968.1994.tb07089.x
    1. Jiao Y., Hasegawa M., Inohara N. (2014). The role of oral pathobionts in dysbiosis during periodontitis development. J. Dent. Res. 93 539–546. 10.1177/0022034514528212
    1. Jin H. J., Bae Y. K., Kim M., Kwon S. J., Jeon H. B., Choi S. J., et al. (2013). Comparative analysis of human mesenchymal stem cells from bone marrow, adipose tissue, and umbilical cord blood as sources of cell therapy. Int. J. Mol. Sci. 14 17986–18001. 10.3390/ijms140917986
    1. Jo Y., Lee H., Kook S., Choung H., Park J., Chung J., et al. (2007). Isolation and characterization of postnatal stem cells from human dental tissues. Tissue Eng. 13 767–773. 10.1089/ten.2006.0192
    1. Kantarci A., Oyaizu K., van Dyke T. E. (2003). Neutrophil-mediated tissue injury in periodontal disease pathogenesis: findings from localized aggressive periodontitis. J. Periodontol. 74 66–75. 10.1902/jop.2003.74.1.66
    1. Kaplan C. W., Ma X., Paranjpe A., Jewett A., Lux R., Kinder-Haake S., et al. (2010). Fusobacterium nucleatum outer membrane proteins Fap2 and RadD induce cell death in human lymphocytes. Infect. Immun. 78 4773–4778. 10.1128/IAI.00567-10
    1. Kebschull M., Papapanou P. (2011). Periodontal microbial complexes associated with specific cell and tissue responses. J. Clin. Periodontol. 38 17–27. 10.1111/j.1600-051X.2010.01668.x
    1. Kim J., Amar S. (2006). Periodontal disease and systemic conditions: a bidirectional relationship. Odontology 94 10–21. 10.1007/s10266-006-0060-6
    1. Kinane D. F., Bartold P. M. (2007). Clinical relevance of the host responses of periodontitis. Periodontol. 2000 43 278–293. 10.1111/j.1600-0757.2006.00169.x
    1. Kinloch A. J., Alzabin S., Brintnell W., Wilson E., Barra L., Wegner N., et al. (2011). Immunization with Porphyromonas gingivalis enolase induces autoimmunity to mammalian α-enolase and arthritis in DR4-IE-transgenic mice. Arthritis Rheum. 63 3818–3823. 10.1002/art.30639
    1. Klein M. I., Goncalves R. B. (2003). Detection of Tannerella forsythensis (Bacteroides forsythus) and Porphyromonas gingivalis by polymerase chain reaction in subjects with different periodontal status. J. Periodontol. 74 798–802. 10.1902/jop.2003.74.6.798
    1. Kolenbrander P. E., Palmer R. J., Jr., Periasamy S., Jakubovics N. S. (2010). Oral multispecies biofilm development and the key role of cell-cell distance. Nat. Rev. Microbiol. 8 471–480. 10.1038/nrmicro2381
    1. Kolte R. A., Kolte A. P., Deshpande N. M. (2014). Assessment and comparison of anemia of chronic disease in healthy subjects and chronic periodontitis patients: a clinical and hematological study. J. Indian Soc. Periodontol. 18 183–186. 10.4103/0972-124X.131321
    1. Konig M. F., Abusleme L., Reinholdt J., Palmer R. J., Teles R. P., Sampson K., et al. (2016). Aggregatibacter actinomycetemcomitans-induced hypercitrullination links periodontal infection to autoimmunity in rheumatoid arthritis. Sci. Transl. Med. 8 369ra176. 10.1126/scitranslmed.aaj1921
    1. Konig M. F., Andrade F. (2016). A critical reappraisal of neutrophil extracellular traps and NETosis mimics based on differential requirements for protein citrullination. Front. Immunol. 7:461. 10.3389/fimmu.2016.00461
    1. Konig M. F., Paracha A. S., Moni M., Bingham C. O., Andrade F. (2014). Defining the role of Porphyromonas gingivalis peptidylarginine deiminase (PPAD) in rheumatoid arthritis through the study of PPAD biology. Ann. Rheum. Dis. 74 2054–2061. 10.1136/annrheumdis-2014-205385
    1. Kopesky P., Tiedemann K., Alkekhia D., Zechner C., Millard B., Schoeberl B., et al. (2014). Autocrine signaling is a key regulatory element during osteoclastogenesis. Biol. Open 3 767–776. 10.1242/bio.20148128
    1. Koziel J., Mydel P., Potempa J. (2014). The link between periodontal disease and rheumatoid arthritis: an updated review. Curr. Rheumatol. Rep. 16:408. 10.1007/s11926-014-0408-9
    1. Kriebel K., Biedermann A., Kreikemeyer B., Lang H. (2013). Anaerobic co-culture of mesenchymal stem cells and anaerobic pathogens-A new in vitro model system. PLOS ONE 8:e78226. 10.1371/journal.pone.0078226
    1. Krishnamurthy A., Joshua V., Haj Hensvold A., Jin T., Sun M., Vivar N., et al. (2016). Identification of a novel chemokine-dependent molecular mechanism underlying rheumatoid arthritis-associated autoantibody-mediated bone loss. Ann. Rheum. Dis. 75 721–729. 10.1136/annrheumdis-2015-208093
    1. Kumar P. S. (2017). From focal sepsis to periodontal medicine: a century of exploring the role of the oral microbiome in systemic disease. J. Physiol. 595 465–476. 10.1113/JP272427
    1. Kuo H. C., Chang L. C., Chen T. C., Lee K. C., Lee K. F., Chen C. N., et al. (2016). Sterol regulatory element-binding protein-1c regulates inflammasome activation in gingival fibroblasts infected with high-glucose-treated Porphyromonas gingivalis. Front. Cell. Infect. Microbiol. 6:195. 10.3389/fcimb.2016.00195
    1. Lakschevitz F. S., Aboodi G. M., Glogauer M. (2013). Oral neutrophil transcriptome changes result in a pro-survival phenotype in periodontal diseases. PLOS ONE 8:e68983. 10.1371/journal.pone.0068983
    1. Li J., Helmerhorst E. J., Leone C. W., Troxler R. F., Yaskell T., Haffajee A. D., et al. (2004). Identification of early microbial colonizers in human dental biofilm. J. Appl. Microbiol. 97 1311–1318. 10.1111/j.1365-2672.2004.02420.x
    1. Li L., Michel R., Cohen J., Decarlo A., Kozarov E. (2008). Intracellular survival and vascular cell-to-cell transmission of Porphyromonas gingivalis. BMC Microbiol. 8:26. 10.1186/1471-2180-8-26
    1. Li T., Khah M. K., Slavnic S., Johansson I., Strömberg N. (2001). Different type 1 fimbrial genes and tropisms of commensal and potentially pathogenic Actinomyces spp. with different salivary acidic proline-rich protein and statherin ligand specificities. Infect. Immun. 69 7224–7233. 10.1128/IAI.69.12.7224-7233.2001
    1. Li X., Kolltveit K. M., Tronstad L., Olsen I. (2000). Systemic diseases caused by oral infection. Clin. Microbiol. Rev. 13 547–558. 10.1128/CMR.13.4.547-558.2000
    1. Li X., Lan H. Y., Huang X. R., Zhang C., Jin L. J. (2013). Expression profile of macrophage migration-inhibitory factor in human gingiva and reconstituted human gingival epithelia stimulated by Porphyromonas gingivalis lipopolysaccharide. J. Periodontal Res. 48 527–532. 10.1111/jre.12035
    1. Liu J., Wang Y., Ouyang X. (2014). Beyond toll-like receptors: Porphyromonas gingivalis induces IL-6, IL-8, and VCAM-1 expression through NOD-mediated NF-κB and ERK signaling pathways in periodontal fibroblasts. Inflammation 37 522–533. 10.1007/s10753-013-9766-0
    1. Liu L., Okada S., Kong X. F., Kreins A. Y., Cypowyj S., Abhyankar A., et al. (2011). Gain-of-function human STAT1 mutations impair IL-17 immunity and underlie chronic mucocutaneous candidiasis. J. Exp. Med. 208 1635–1648. 10.1084/jem.20110958
    1. Lundberg K., Kinloch A., Fisher B. A., Wegner N., Wait R., Charles P., et al. (2008). Antibodies to citrullinated α-enolase peptide 1 are specific for rheumatoid arthritis and cross-react with bacterial enolase. Arthritis Rheum. 58 3009–3019. 10.1002/art.23936
    1. Madianos P. N., Papapanou P. N., Sandros J. (1997). Porphyromonas gingivalis infection of oral epithelium inhibits neutrophil transepithelial migration. Infect. Immun. 65 3983–3990.
    1. Maekawa T., Krauss J. L., Abe T., Jotwani R., Triantafilou M., Triantafilou K., et al. (2014). Porphyromonas gingivalis manipulates complement and TLR signaling to uncouple bacterial clearance from inflammation and promote dysbiosis. Cell Host Microbe 15 768–778. 10.1016/j.chom.2014.05.012
    1. Mahanonda R., Sa-Ard-Iam N., Montreekachon P., Pimkhaokham A., Yongvanichit K., Fukuda M. M., et al. (2007). IL-8 and IDO expression by human gingival fibroblasts via TLRs. J. Immunol. 178 1151–1157. 10.4049/jimmunol.178.2.1151
    1. Mangat P., Wegner N., Venables P. J., Potempa J. (2010). Bacterial and human peptidylarginine deiminases: targets for inhibiting the autoimmune response in rheumatoid arthritis? Arthritis Res. Ther. 12:209. 10.1186/ar3000
    1. Marchant C., Smith M. D., Proudman S., Haynes D. R., Bartold P. M. (2013). Effect of Porphyromonas gingivalis on citrullination of proteins by macrophages in vitro. J. Periodontol. 84 1272–1280. 10.1902/jop.2012.120103
    1. Maresz K. J., Hellvard A., Sroka A., Adamowicz K., Bielecka E., Koziel J., et al. (2013). Porphyromonas gingivalis facilitates the development and progression of destructive arthritis through its unique bacterial peptidylarginine deiminase (PAD). PLOS Pathog. 9:e1003627. 10.1371/journal.ppat.1003627
    1. Mark Welch J. L., Rossetti B. J., Rieken C. W., Dewhirst F. E., Borisy G. G. (2016). Biogeography of a human oral microbiome at the micron scale. Proc. Natl. Acad. Sci. U.S.A. 113 E791–E800. 10.1073/pnas.1522149113
    1. McGraw W. T., Potempa J., Farley D., Travis J. (1999). Purification, characterization, and sequence analysis of a potential virulence factor from Porphyromonas gingivalis, peptidylarginine deiminase. Infect. Immun. 67 3248–3256.
    1. Mettraux G. R., Gusberti F. A., Graf H. (1984). Oxygen tension (pO2) in untreated human periodontal pockets. J. Periodontol. 55 516–521. 10.1902/jop.1984.55.9.516
    1. Mikuls T. R., Payne J. B., Reinhardt R. A., Thiele G. M., Maziarz E., Cannella A. C., et al. (2009). Antibody responses to Porphyromonas gingivalis in subjects with rheumatoid arthritis and periodontitis. Int. Immunopharmacol. 9 38–42. 10.1016/j.intimp.2008.09.008
    1. Mikuls T. R., Payne J. B., Yu F., Thiele G. M., Reynolds R. J., Cannon G. W., et al. (2014). Periodontitis and Porphyromonas gingivalis in patients with rheumatoid arthritis. Arthritis Rheumatol. 66 1090–1100. 10.1002/art.38348
    1. Miura M., Gronthos S., Zhao M., Lu B., Fisher L. W., Robey P. G., et al. (2003). SHED: stem cells from human exfoliated deciduous teeth. Proc. Natl. Acad. Sci. U.S.A. 100 5807–5812. 10.1073/pnas.0937635100
    1. Moffatt C. E., Lamont R. J. (2011). Porphyromonas gingivalis induction of microRNA-203 expression controls suppressor of cytokine signaling 3 in gingival epithelial cells. Infect. Immun. 79 2632–2637. 10.1128/IAI.00082-11
    1. Montebugnoli L., Servidio D., Miaton R. A., Prati C., Tricoci P., Melloni C., et al. (2005). Periodontal health improves systemic inflammatory and haemostatic status in subjects with coronary heart disease. J. Clin. Periodontol. 32 188–192. 10.1111/j.1600-051X.2005.00641.x
    1. Montgomery A. B., Kopec J., Shrestha L., Thezenas M. L., Burgess-Brown N. A., Fischer R., et al. (2016). Crystal structure of Porphyromonas gingivalis peptidylarginine deiminase: implications for autoimmunity in rheumatoid arthritis. Ann. Rheum. Dis. 75 1255–1261. 10.1136/annrheumdis-2015-207656
    1. Morandini A. C., Chaves Souza P. P., Ramos-Junior E. S., Brozoski D. T., Sipert C. R., Souza Costa C. A., et al. (2013). Toll-like receptor 2 knockdown modulates interleukin (IL)-6 and IL-8 but not stromal derived factor-1 (SDF-1/CXCL12) in human periodontal ligament and gingival fibroblasts. J. Periodontol. 84 535–544. 10.1902/jop.2012.120177
    1. Moscarello M. A., Mastronardi F. G., Wood D. D. (2007). The role of citrullinated proteins suggests a novel mechanism in the pathogenesis of multiple sclerosis. Neurochem. Res. 32 251–256. 10.1007/s11064-006-9144-5
    1. 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. Sci. Transl. Med. 6:229ra40. 10.1126/scitranslmed.3007696
    1. Moutsopoulos N. M., Lionakis M. S., Hajishengallis G. (2015). Inborn errors in immunity: unique natural models to dissect oral immunity. J. Dent. Res. 94 753–758. 10.1177/0022034515583533
    1. Muzio M., Mantovani A. (2000). Toll-like receptors. Microbes Infect. 2 251–255. 10.1016/S1286-4579(00)00303-8
    1. Mysak J., Podzimek S., Sommerova P., Lyuya-Mi Y., Bartova J., Janatova T., et al. (2014). Porphyromonas gingivalis: major periodontopathic pathogen overview. J. Immunol. Res. 2014:476068. 10.1155/2014/476068
    1. Navarro-Millán I., Darrah E., Westfall A. O., Mikuls T. R., Reynolds R. J., Danila M. I., et al. (2016). Association of anti-peptidyl arginine deiminase antibodies with radiographic severity of rheumatoid arthritis in African Americans. Arthritis Res. Ther. 18:241. 10.1186/s13075-016-1126-7
    1. Nelson-Filho P., Borba I. G., Mesquita K. S., Silva R. A., Queiroz A. M., Silva L. A. (2013). Dynamics of microbial colonization of the oral cavity in newborns. Braz. Dent. J. 24 415–419. 10.1590/0103-6440201302266
    1. Nesbitt W. E., Beem J. E., Leung K. P., Clark W. B. (1992). Isolation and characterization of Actinomyces viscosus mutants defective in binding salivary proline-rich proteins. Infect. Immun. 60 1095–1100.
    1. Nesse W., Westra J., van der Wal J. E., Abbas F., Nicholas A. P., Vissink A., et al. (2012). The periodontium of periodontitis patients contains citrullinated proteins which may play a role in ACPA (anti-citrullinated protein antibody) formation. J. Clin. Periodontol. 39 599–607. 10.1111/j.1600-051X.2012.01885.x
    1. O’Brien-Simpson N. M., Pathirana R. D., Walker G. D., Reynolds E. C. (2009). Porphyromonas gingivalis RgpA-Kgp proteinase-adhesin complexes penetrate gingival tissue and induce proinflammatory cytokines or apoptosis in a concentration-dependent manner. Infect. Immun. 77 1246–1261. 10.1128/IAI.01038-08
    1. O’Connell R. M., Taganov K. D., Boldin M. P., Cheng G., Baltimore D. (2007). MicroRNA-155 is induced during the macrophage inflammatory response. Proc. Natl. Acad. Sci. U.S.A. 104 1604–1609. 10.1073/pnas.0610731104
    1. Ohlrich E. J., Cullinan M. P., Seymour G. J. (2009). The immunopathogenesis of periodontal disease. Aust. Dent. J. 54 S2–S10. 10.1111/j.1834-7819.2009.01139.x
    1. Okahashi N., Nakata M., Terao Y., Isoda R., Sakurai A., Sumitomo T., et al. (2011). Pili of oral Streptococcus sanguinis bind to salivary amylase and promote the biofilm formation. Microb. Pathog. 50 148–154. 10.1016/j.micpath.2011.01.005
    1. Oli M. W., McArthur W. P., Brady L. J. (2006). A whole cell BIAcore assay to evaluate P1-mediated adherence of Streptococcus mutans to human salivary agglutinin and inhibition by specific antibodies. J. Microbiol. Methods. 65 503–511. 10.1016/j.mimet.2005.09.011
    1. Ortiz P., Bissada N. F., Palomo L., Han Y. W., Al-Zahrani M. S., Panneerselvam A., et al. (2009). Periodontal therapy reduces the severity of active rheumatoid arthritis in patients treated with or without tumor necrosis factor inhibitors. J. Periodontol. 80 535–540. 10.1902/jop.2009.080447
    1. Palm E., Demirel I., Bengtsson T., Khalaf H. (2015). The role of toll-like and protease-activated receptors in the expression of cytokines by gingival fibroblasts stimulated with the periodontal pathogen Porphyromonas gingivalis. Cytokine 76 424–432. 10.1016/j.cyto.2015.08.263
    1. Pathirana R. D., O’Brien-Simpson N. M., Visvanathan K., Hamilton J. A., Reynolds E. C. (2008). The role of the RgpA-Kgp proteinase-adhesin complexes in the adherence of Porphyromonas gingivalis to fibroblasts. Microbiology 154 2904–2911. 10.1099/mic.0.2008/019943-0
    1. Pihlstrom B. L., Michalowicz B. S., Johnson N. W. (2005). Periodontal diseases. Lancet 366 1809–1820. 10.1016/S0140-6736(05)67728-8
    1. Pinnock A., Murdoch C., Moharamzadeh K., Whawell S., Douglas C. W. (2014). Characterisation and optimisation of organotypic oral mucosal models to study Porphyromonas gingivalis invasion. Microbes Infect. 16 310–319. 10.1016/j.micinf.2014.01.004
    1. Promsudthi A., Poomsawat S., Limsricharoen W. (2014). The role of Toll-like receptor 2 and 4 in gingival tissues of chronic periodontitis subjects with type 2 diabetes. J. Periodontal Res. 49 346–354. 10.1111/jre.12112
    1. Pyrc K., Milewska A., Kantyka T., Sroka A., Maresz K., Kozieł J., et al. (2013). Inactivation of epidermal growth factor by Porphyromonas gingivalis as a potential mechanism for periodontal tissue damage. Infect. Immun. 81 55–64. 10.1128/IAI.00830-12
    1. Quirke A. M., Lugli E. B., Wegner N., Hamilton B. C., Charles P., Chowdhury M., et al. (2014). Heightened immune response to autocitrullinated Porphyromonas gingivalis peptidylarginine deiminase: a potential mechanism for breaching immunologic tolerance in rheumatoid arthritis. Ann. Rheum. Dis. 73 263–269. 10.1136/annrheumdis-2012-202726
    1. Ramsey M. M., Rumbaugh K. P., Whiteley M. (2011). Metabolite cross-feeding enhances virulence in a model polymicrobial infection. PLOS Pathog. 7:e1002012. 10.1371/journal.ppat.1002012
    1. Reichert S., Haffner M., Keyßer G., Schäfer C., Stein J. M., Schaller H.-G., et al. (2013). Detection of oral bacterial DNA in synovial fluid. J. Clin. Periodontol. 40 591–598. 10.1111/jcpe.12102
    1. Restaino C. G., Chaparro A., Valenzuela M., Vernal R., Silva A., Puente J., et al. (2007). Stimulatory response of neutrophils from periodontitis patients with periodontal pathogens. Oral Dis. 13 474–481. 10.1111/j.1601-0825.2006.01323.x
    1. Rodriguez B., Stitt B. L., Ash D. E. (2009). Expression of peptidylarginine deiminase from Porphyromonas gingivalis in Escherichia coli: enzyme purification and characterization. Arch. Biochem. Biophys. 488 14–22. 10.1016/j.abb.2009.06.010
    1. Romero V., Fert-Bober J., Nigrovic P. A., Darrah E., Haque U. J., Lee D. M., et al. (2013). Immune-mediated pore-forming pathways induce cellular hypercitrullination and generate citrullinated autoantigens in rheumatoid arthritis. Sci. Transl. Med. 5:209ra150. 10.1126/scitranslmed.3006869
    1. Rosenstein E. D., Greenwald R. A., Kushner L. J., Weissmann G. (2004). Hypothesis: the humoral immune response to oral bacteria provides a stimulus for the development of rheumatoid arthritis. Inflammation 28 311–318. 10.1007/s10753-004-6641-z
    1. Rose A. S., Hildebrand P. W. (2015). NGL Viewer: a web application for molecular visualization. Nucl. Acids Res. 43 W576–W579. 10.1093/nar/gkv402
    1. Rotimi V. O., Duerden B. I. (1981). The development of the bacterial flora in normal neonates. J. Med. Microbiol. 14 51–62. 10.1099/00222615-14-1-51
    1. Saito A., Inagaki S., Kimizuka R., Okuda K., Hosaka Y., Nakagawa T., et al. (2008). Fusobacterium nucleatum enhances invasion of human gingival epithelial and aortic endothelial cells by Porphyromonas gingivalis. FEMS Immunol. Med. Microbiol. 54 349–355. 10.1111/j.1574-695X.2008.00481.x
    1. Schaefer A. S., Jochens A., Dommisch H., Graetz C., Jockel-Schneider Y., Harks I., et al. (2014). A large candidate-gene association study suggests genetic variants at IRF5 and PRDM1 to be associated with aggressive periodontitis. J. Clin. Periodontol. 41 1122–1131. 10.1111/jcpe.12314
    1. Schellekens G. A., De Jong B. A., van den Hoogen F. H., van de Putte L. B., van Venrooij W. J. (1998). Citrulline is an essential constituent of antigenic determinants recognized by rheumatoid arthritis-specific autoantibodies. J. Clin. Invest. 101 273–281. 10.1172/JCI1316
    1. Schellekens G. A., Visser H., de Jong B. A., van den Hoogen F. H., Hazes J. M., Breedveld F. C., et al. (2000). The diagnostic properties of rheumatoid arthritis antibodies recognizing a cyclic citrullinated peptide. Arthritis Rheum. 43 155–163. 10.1002/1529-0131(200001)43:1<155::AID-ANR20>;2-3
    1. Scheres N., Crielaard W. (2013). Gingival fibroblast responsiveness is differentially affected by Porphyromonas gingivalis: implications for the pathogenesis of periodontitis. Mol. Oral Microbiol. 28 204–218. 10.1111/omi.12016
    1. Scheres N., Laine M. L., de Vries T. J., Everts V., van Winkelhoff A. J. (2009). Gingival and periodontal ligament fibroblasts differ in their inflammatory response to viable Porphyromonas gingivalis. J. Periodontal Res. 45 262–270. 10.1111/j.1600-0765.2009.01229.x
    1. Segal A. W. (2005). How neutrophils kill microbes. Annu. Rev. Immunol. 23 197–223. 10.1146/annurev.immunol.23.021704.115653
    1. Seo B., Miura M., Gronthos S., Bartold P. M., Batouli S., Brahim J., et al. (2004). Investigation of multipotent postnatal stem cells from human periodontal ligament. Lancet 364 149–155. 10.1016/S0140-6736(04)16627-0
    1. Seymour G. J., Powell R. N., Davies W. I. (1979). The immunopathogenesis of progressive chronic inflammatory periodontal disease. J. Oral Pathol. 8 249–265. 10.1111/j.1600-0714.1979.tb01826.x
    1. Slots J. (1977). The predominant cultivable microflora of advanced periodontitis. Scand. J. Dent. Res. 85 114–121. 10.1111/j.1600-0722.1977.tb00541.x
    1. Socransky S. S., Haffajee A. D., Cugini M. A., Smith C., Kent R. L., Jr. (1998). Microbial complexes in subgingival plaque. J. Clin. Periodontol. 25 134–144. 10.1111/j.1600-051X.1998.tb02419.x
    1. Sohn D. H., Rhodes C., Onuma K., Zhao X., Sharpe O., Gazitt T., et al. (2015). Local Joint inflammation and histone citrullination in a murine model of the transition from preclinical autoimmunity to inflammatory arthritis. Arthritis Rheumatol. 67 2877–2887. 10.1002/art.39283
    1. Sonoyama W., Liu Y., Fang D., Yamaza T., Seo B., Zhang C., et al. (2006). Mesenchymal stem cell-mediated functional tooth regeneration in swine. PLOS ONE 1:e79. 10.1371/journal.pone.0000079
    1. Sonoyama W., Liu Y., Yamaza T., Tuan R. S., Wang S., Shi S., et al. (2008). Characterization of the apical papilla and its residing stem cells from human immature permanent teeth: a pilot study. J. Endod. 34 166–171. 10.1016/j.joen.2007.11.021
    1. Souza P. P., Palmqvist P., Lundgren I., Lie A., Costa-Neto C. M., Lundberg P., et al. (2010). Stimulation of IL-6 cytokines in fibroblasts by toll-like receptors 2. J. Dent. Res. 89 802–807. 10.1177/0022034510366898
    1. Spengler J., Lugonja B., Ytterberg A. J., Zubarev R. A., Creese A. J., Pearson M. J., et al. (2015). Release of active peptidyl arginine deiminases by neutrophils can explain production of extracellular citrullinated autoantigens in rheumatoid arthritis synovial fluid. Arthritis Rheumatol. 67 3135–3145. 10.1002/art.39313
    1. Stein J. M., Machulla H. K., Smeets R., Lampert F., Reichert S. (2008). Human leukocyte antigen polymorphism in chronic and aggressive periodontitis among Caucasians: a meta-analysis. J. Clin. Periodontol. 35 183–192. 10.1111/j.1600-051X.2007.01189.x
    1. 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. Res. 85 524–529. 10.1177/154405910608500609
    1. Sun J., Nemoto E., Hong G., Sasaki K. (2016). Modulation of stromal cell-derived factor 1 alpha (SDF-1α) and its receptor CXCR4 in Porphyromonas gingivalis-induced periodontal inflammation. BMC Oral Health 17:26. 10.1186/s12903-016-0250-8
    1. Tavian M., Zheng B., Oberlin E., Crisan M., Sun B., Huard J., et al. (2006). The vascular wall as a source of stem cells. Ann. N. Y. Acad. Sci. 1044 41–50. 10.1196/annals.1349.006
    1. Tzach-Nahman R., Nashef R., Fleissig O., Palmon A., Shapira L., Wilensky A., et al. (2017). Oral fibroblasts modulate the macrophage response to bacterial challenge. Sci. Rep. 7:11516. 10.1038/s41598-017-11771-3
    1. Uematsu H., Hoshino E. (1992). Predominant obligate anaerobes in human periodontal pockets. J. Periodontal Res. 27 15–19. 10.1111/j.1600-0765.1992.tb02080.x
    1. van Dyke T. E., Sheilesh D. (2005). Risk factors for periodontitis. J. Int. Acad. Periodontol. 7 3–7.
    1. Vossenaar E. R., van Venrooij W. J. (2004). Citrullinated proteins: sparks that may ignite the fire in rheumatoid arthritis. Arthritis Res. Ther. 6 107–111. 10.1186/ar1184
    1. Vossenaar E. R., Zendman A. J., Van Venrooij W. J., Pruijn G. J. (2003). PAD, a growing family of citrullinating enzymes: genes, features and involvement in disease. Bioessays 25 1106–1118. 10.1002/bies.10357
    1. Waddington R. J., Moseley R., Embery G. (2000). Reactive oxygen species: a potential role in the pathogenesis of periodontal diseases. Oral Dis. 6 138–151. 10.1111/j.1601-0825.2000.tb00325.x
    1. Wade W. G. (2013). The oral microbiome in health and disease. Pharmacol. Res. 69 137–143. 10.1016/j.phrs.2012.11.006
    1. Weerkamp A. H., Uyen H. M., Busscher H. J. (1988). Effect of zeta potential and surface energy on bacterial adhesion to uncoated and saliva-coated human enamel and dentin. J. Dent. Res. 67 1483–1487. 10.1177/00220345880670120801
    1. Wegner N., Wait R., Sroka A., Eick S., Nguyen K. A., Lundberg K., et al. (2010). Peptidylarginine deiminase from Porphyromonas gingivalis citrullinates human fibrinogen and α-enolase: implications for autoimmunity in rheumatoid arthritis. Arthritis Rheum. 62 2662–2672. 10.1002/art.27552
    1. Wessel A. K., Arshad T. A., Fitzpatrick M., Connell J. L., Bonnecaze R. T., Shear J. B., et al. (2014). Oxygen limitation within a bacterial aggregate. mBio 5:e00992. 10.1128/mBio.00992-14
    1. Witalison E. E., Thompson P. R., Hofseth L. J. (2015). Protein arginine deiminases and associated citrullination: physiological functions and diseases associated with dysregulation. Curr. Drug Targets 16 700–710. 10.2174/1389450116666150202160954
    1. Yang H. W., Huang Y. F., Chou M. Y. (2004). Occurrence of Porphyromonas gingivalis and Tannerella forsythensis in periodontally diseased and healthy subjects. J. Periodontol. 75 1077–1083. 10.1902/jop.2004.75.8.1077
    1. Yano-Higuchi K., Takamatsu N., He T., Umeda M., Ishikawa I. (2000). Prevalence of Bacteroides forsythus, Porphyromonas gingivalis and Actinobacillus actinomycetemcomitans in subgingival microflora of Japanese patients with adult and rapidly progressive periodontitis. J. Clin. Periodontol. 27 597–602. 10.1034/j.1600-051x.2000.027008597.x
    1. Zarco M. F., Vess T. J., Ginsburg G. S. (2012). The oral microbiome in health and disease and the potential impact on personalized dental medicine. Oral Dis. 18 109–120. 10.1111/j.1601-0825.2011.01851.x
    1. Zhang J., Dai J., Zhao E., Lin Y., Zeng L., Chen J., et al. (2004). cDNA cloning, gene organization and expression analysis of human peptidylarginine deiminase type VI. Acta Biochim. Pol. 51 1051–1058.
    1. Zhang Q., Shi S., Liu Y., Uyanne J., Shi Y., Le A. (2009). Mesenchymal stem cells derived from human gingiva are capable of immunomodulatory functions and ameliorate inflammation-related tissue destruction in experimental colitis. J. Immunol. 183 7787–7798. 10.4049/jimmunol.0902318
    1. Zhang W., Ju J., Rigney T., Tribble G. (2014). Porphyromonas gingivalis infection increases osteoclastic bone resorption and osteoblastic bone formation in a periodontitis mouse model. BMC Oral Health 14:89. 10.1186/1472-6831-14-89
    1. Zhu L., Kreth J. (2012). The role of hydrogen peroxide in environmental adaptation of oral microbial communities. Oxid. Med. Cell. Longev. 2012:717843. 10.1155/2012/717843

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