Porphyromonas gingivalis virulence factors involved in subversion of leukocytes and microbial dysbiosis

Virulence

Volumn 6, Issue 3, 2015, Pages 236-243

  Zenobia, Camille ^a   Hajishengallis, George ^a  

^a UNIVERSITY OF PENNSYLVANIA   (United States)

Author keywords

Dysbiosis; Immune subversion; Inflammation leukocytes; P. gingivalis; Periodontitis

Indexed keywords

CASPASE 11; CHEMOKINE RECEPTOR CXCR4; COMPLEMENT COMPONENT C5A RECEPTOR; HEMIN; INTERCELLULAR ADHESION MOLECULE 3; INTERLEUKIN 17; INTERLEUKIN 18; INTERLEUKIN 1BETA; INTERLEUKIN 8; MYELOID DIFFERENTIATION FACTOR 88; PHOSPHATIDYLINOSITOL 3 KINASE; TOLL LIKE RECEPTOR 2; TOLL LIKE RECEPTOR 4; TRANSCRIPTION FACTOR RELA; VIRULENCE FACTOR;

BACTERIAL COLONIZATION; BACTERIAL LOAD; BACTERIAL VIRULENCE; CD4+ T LYMPHOCYTE; CD8+ T LYMPHOCYTE; DYSBIOSIS; HUMAN; IMMUNE RESPONSE; MICROBIAL COMMUNITY; NONHUMAN; PERIODONTITIS; PHAGOCYTOSIS; PORPHYROMONAS GINGIVALIS; PROTEIN EXPRESSION; REVIEW; SIGNAL TRANSDUCTION; TEMPERATURE; ANIMAL; COMPLICATION; GENETICS; HOST PATHOGEN INTERACTION; IMMUNOLOGY; LEUKOCYTE; MACROPHAGE; MICROBIOLOGY; MOUTH; PATHOGENICITY; PHYSIOLOGY;

BACTERIA (MICROORGANISMS); PORPHYROMONAS GINGIVALIS;

ANIMALS; DYSBIOSIS; HOST-PATHOGEN INTERACTIONS; HUMANS; LEUKOCYTES; MACROPHAGES; MOUTH; PERIODONTITIS; PORPHYROMONAS GINGIVALIS; VIRULENCE FACTORS;

EID: 84927771860     PISSN: 21505594     EISSN: 21505608     Source Type: Journal    
DOI: 10.1080/21505594.2014.999567     Document Type: Review

References (90)

1. Pihlstrom BL, Michalowicz BS, Johnson NW. Periodontal diseases. Lancet 2005; 366:1809-20; PMID:16298220; http://dx.doi.org/10.1016/S0140- 6736(05)67728-8
2. Hajishengallis G. Periodontitis: from microbial immune subversion to systemic inflammation. Nat Rev Immunol 2015; 15(1):30-44; PMID:25534621; http://dx.doi.org/10.1038/nri3785
3. Abusleme L, Dupuy AK, Dutzan N, Silva N, Burleson JA, Strausbaugh LD, Gamonal J, Diaz PI. The subgingival microbiome in health and periodontitis and its relationship with community biomass and inflammation. ISME J 2013; 7:1016-25; PMID:23303375; http://dx.doi.org/10.1038/ismej.2012.174
4. Jorth P, Turner KH, Gumus P, Nizam N, Buduneli N, Whiteley M. Metatranscriptomics of the human oral microbiome during health and disease. MBio 2014; 5: e01012-14; PMID:24692635; http://dx.doi.org/ 10.1128/mBio.01012-14
5. Hajishengallis G, Lamont RJ. Beyond the red complex and into more complexity: The Polymicrobial Synergy and Dysbiosis (PSD) model of periodontal disease etiology. Mol Oral Microbiol 2012; 27:409-19; PMID:23134607; http://dx.doi.org/10.1111/j.2041- 1014.2012.00663.x
6. Lamont RJ, Hajishengallis G. Polymicrobial synergy and dysbiosis in inflammatory disease. Trends Mol Med 2014; PMID:25498392; doi:10.1016/j. molmed.2014.11.004 (Epub ahead of print)
7. Rosier BT, de Jager M, Zaura E, Krom BP. Historical and contemporary hypotheses on the development of oral diseases: are we there yet? Front Cell Infect Microbiol 2014; 4:92; PMID:25077073; http://dx.doi.org/ 10.3389/fcimb.2014.00092
8. Costalonga M, Herzberg MC. The oral microbiome and the immunobiology of periodontal disease and caries. Immunol Lett 2014; 162(2 Pt A):22-38; PMID:25447398; doi:10.1016/j.imlet.2014.08.017 (Epub ahead of print)
9. Socransky SS, Haffajee AD, Cugini MA, Smith C, Kent RL, Jr. Microbial complexes in subgingival plaque. J Clin Periodontol 1998; 25:134-44; PMID:9495612; http://dx.doi.org/10.1111/j.1600- 051X.1998.tb02419.x
10. Hajishengallis G, Liang S, Payne MA, Hashim A, Jotwani R, Eskan MA, McIntosh ML, Alsam A, Kirkwood KL, Lambris JD, et al. Low-abundance biofilm species orchestrates inflammatory periodontal disease through the commensal microbiota and complement. Cell Host Microbe 2011; 10:497-506; PMID:22036469; http:// dx.doi.org/10.1016/j.chom.2011.10.006
11. Hajishengallis G, Darveau RP, Curtis MA. The keystone- pathogen hypothesis. Nat Rev Microbiol 2012; 10:717-25; PMID:22941505; http://dx.doi.org/ 10.1038/nrmicro2873
12. Darveau RP. The oral microbial consortium’s interaction with the periodontal innate defense system. DNA Cell Biol 2009; 28:389-95; PMID:19435427; http:// dx.doi.org/10.1089/dna.2009.0864
13. Kumar PS, Leys EJ, Bryk JM, Martinez FJ, Moeschberger ML, Griffen AL. Changes in periodontal health status are associated with bacterial community shifts as assessed by quantitative 16S cloning and sequencing. J Clin Microbiol 2006; 44:3665-73; PMID:17021095; http://dx.doi.org/10.1128/JCM.00317-06
14. Doungudomdacha S, Rawlinson A, Douglas CW. Enumeration of Porphyromonas gingivalis, Prevotella intermedia and Actinobacillus actinomycetemcomitans in subgingival plaque samples by a quantitative-competitive PCR method. J Med Microbiol 2000; 49:861-74; PMID:11023183
15. Page RC, Lantz MS, Darveau R, Jeffcoat M, Mancl L, Houston L, Braham P, Persson GR. Immunization of Macaca fascicularis against experimental periodontitis using a vaccine containing cysteine proteases purified from Porphyromonas gingivalis. Oral Microbiol Immunol 2007; 22:162-8; PMID:17488441; http://dx.doi. org/10.1111/j.1399-302X.2007.00337.x
16. Hajishengallis G. Immunomicrobial pathogenesis of periodontitis: keystones, pathobionts, and host response. Trends Immunol 2014; 35:3-11; PMID:24269668; http://dx.doi.org/10.1016/j. it.2013.09.001
17. Kumar PS. Smoking and the subgingival ecosystem: a pathogen-enriched community. Future Microbiol 2012; 7:917-9; PMID:22913349; http://dx.doi.org/ 10.2217/fmb.12.71
18. Stabholz A, Soskolne WA, Shapira L. Genetic and environmental risk factors for chronic periodontitis and aggressive periodontitis. Periodontol 2000 2010; 53:138-53; PMID:20403110; http://dx.doi.org/ 10.1111/j.1600-0757.2010.00340.x
19. Zhou Q, Leeman SE, Amar S. Signaling mechanisms in the restoration of impaired immune function due to diet-induced obesity. Proc Natl Acad Sci U S A 2011; 108:2867-72; PMID:21282635; http://dx.doi.org/ 10.1073/pnas.1019270108
20. Divaris K, Monda KL, North KE, Olshan AF, Reynolds LM, Hsueh WC, Lange EM, Moss K, Barros SP, Weyant RJ, et al. Exploring the genetic basis of chronic periodontitis: a genome-wide association study. Hum Mol Genet 2013; 22:2312-24; PMID:23459936; http://dx.doi.org/10.1093/hmg/ddt065
21. Bagaitkar J, Williams LR, Renaud DE, Bemakanakere MR, Martin M, Scott DA, Demuth DR. Tobaccoinduced alterations to Porphyromonas gingivalis-host interactions. Environ Microbiol 2009; 11:1242-53; PMID:19175666; http://dx.doi.org/10.1111/j.1462- 2920.2008.01852.x
22. Xie H, Cai S, Lamont RJ. Environmental regulation of fimbrial gene expression in Porphyromonas gingivalis. Infect Immun 1997; 65:2265-71; PMID:9169762
23. Al-Qutub MN, Braham PH, Karimi-Naser LM, Liu X, Genco CA, Darveau RP. Hemin-dependent modulation of the lipid A structure of Porphyromonas gingivalis lipopolysaccharide. Infect Immun 2006; 74:4474-85; PMID:16861633; http://dx.doi.org/10.1128/ IAI.01924-05
24. Curtis MA, Percival RS, Devine D, Darveau RP, Coats SR, Rangarajan M, Tarelli E, Marsh PD. Temperaturedependent modulation of Porphyromonas gingivalis lipid A structure and interaction with the innate host defenses. Infect Immun 2011; 79:1187-93; PMID: 21220483; http://dx.doi.org/10.1128/IAI.00900-10
25. Roy F, Vanterpool E, Fletcher HM. HtrA in Porphyromonas gingivalis can regulate growth and gingipain activity under stressful environmental conditions. Microbiology 2006; 152:3391-8; PMID:17074908; http://dx.doi.org/10.1099/mic.0.29147-0
26. Maekawa T, Krauss JL, Abe T, Jotwani R, Triantafilou M, Triantafilou K, Hashim A, Hoch S, Curtis MA, Nussbaum G, et al. Porphyromonas gingivalis manipulates complement and TLR signaling to uncouple bacterial clearance from inflammation and promote dysbiosis. Cell Host Microbe 2014; 15:768-78; PMID:24922578; http://dx.doi.org/10.1016/j. chom.2014.05.012
27. Darveau RP, Belton CM, Reife RA, Lamont RJ. Local chemokine paralysis, a novel pathogenic mechanism for Porphyromonas gingivalis. Infect Immun 1998; 66:1660-5; PMID:9529095
28. Dewhirst FE, Chen T, Izard J, Paster BJ, Tanner AC, Yu WH, Lakshmanan A, Wade WG. The human oral microbiome. J Bacteriol 2010; 192:5002-17; PMID: 20656903; http://dx.doi.org/10.1128/JB.00542-10
29. Tonetti MS, Imboden MA, Lang NP. Neutrophil migration into the gingival sulcus is associated with transepithelial gradients of interleukin-8 and ICAM-1. J Periodontol 1998; 69:1139-47; PMID:9802714; http://dx.doi.org/10.1902/jop.1998.69.10.1139
30. Darveau RP. Periodontitis: a polymicrobial disruption of host homeostasis. Nat Rev Microbiol 2010; 8:481-90; PMID:20514045; http://dx.doi.org/ 10.1038/nrmicro2337
31. Ryder MI. Comparison of neutrophil functions in aggressive and chronic periodontitis. Periodontol 2000 2010; 53:124-37; PMID:20403109; http://dx.doi.org/ 10.1111/j.1600-0757.2009.00327.x
32. Takeuchi H, Hirano T, Whitmore SE, Morisaki I, Amano A, Lamont RJ. The serine phosphatase SerB of Porphyromonas gingivalis suppresses IL-8 production by dephosphorylation of NF-kB RelA/p65. PLoS Pathog 2013; 9:e1003326; PMID:23637609; http://dx.doi. org/10.1371/journal.ppat.1003326
33. Bainbridge B, Verma RK, Eastman C, Yehia B, Rivera M, Moffatt C, Bhattacharyya I, Lamont RJ, Kesavalu L. Role of Porphyromonas gingivalis phosphoserine phosphatase enzyme SerB in inflammation, immune response, and induction of alveolar bone resorption in rats. Infect Immun 2010; 78:4560-9; PMID:20805334; http://dx.doi.org/ 10.1128/IAI.00703-10
34. Moutsopoulos NM, Konkel J, Sarmadi M, Eskan MA, Wild T, Dutzan N, Abusleme L, Zenobia C, Hosur KB, Abe T, et al. Defective neutrophil recruitment in leukocyte adhesion deficiency type I disease causes local IL-17-driven inflammatory bone loss. Sci Transl Med 2014; 6:229ra40; PMID:24670684
35. Phillipson M, Kubes P. The neutrophil in vascular inflammation. Nat Med 2011; 17:1381-90; PMID:22064428; http://dx.doi.org/10.1038/nm.2514
36. Kolaczkowska E, Kubes P. Neutrophil recruitment and function in health and inflammation. Nat Rev Immunol 2013; 13:159-75; PMID:23435331; http://dx.doi. org/10.1038/nri3399
37. Wingrove JA, DiScipio RG, Chen Z, Potempa J, Travis J, Hugli TE. Activation of complement components C3 and C5 by a cysteine proteinase (gingipain-1) from Porphyromonas (Bacteroides) gingivalis. J Biol Chem 1992; 267:18902-7; PMID:1527018
38. Chapple CC, Srivastava M, Hunter N. Failure of macrophage activation in destructive periodontal disease. J Pathol 1998; 186:281-6; PMID:10211117; http://dx. doi.org/10.1002/(SICI)1096-9896(1998110) 186:3%3c281::AID-PATH200%3e3.0.CO;2-7
39. Hasturk H, Kantarci A, Van Dyke TE. Oral inflammatory diseases and systemic inflammation: role of the macrophage. Front Immunol 2012; 3:118; PMID: 22623923; http://dx.doi.org/10.3389/fimmu. 2012.00118
40. Franchi L, Eigenbrod T, Munoz-Planillo R, Nunez G. The inflammasome: a caspase-1-activation platform that regulates immune responses and disease pathogenesis. Nat Immunol 2009; 10:241-7; PMID:19221555; http://dx.doi.org/10.1038/ni.1703
41. Hajishengallis G, Wang M, Harokopakis E, Triantafilou M, Triantafilou K. Porphyromonas gingivalis fimbriae proactively modulate b2 integrin adhesive activity and promote binding to and internalization by macrophages. Infect Immun 2006; 74:5658-66; PMID: 16988241; http://dx.doi.org/10.1128/IAI.00784-06
42. Wang M, Hajishengallis G. Lipid raft-dependent uptake, signalling and intracellular fate of Porphyromonas gingivalis in mouse macrophages. Cell Microbiol 2008; 10:2029-42; PMID:18547335; http://dx.doi. org/10.1111/j.1462-5822.2008.01185.x
43. Hajishengallis G, McIntosh ML, Nishiyama SI, Yoshimura F. Mechanism and implications of CXCR4- mediated integrin activation by Porphyromonas gingivalis. Mol Oral Microbiol 2013; 28:239-249; http://dx. doi.org/10.1111/omi.12021
44. Hajishengallis G, Wang M, Liang S, Triantafilou M, Triantafilou K. Pathogen induction of CXCR4/TLR2 cross-talk impairs host defense function. Proc Natl Acad Sci U S A 2008; 105:13532-7; PMID:18765807; http://dx.doi.org/10.1073/pnas.0803852105
45. Hajishengallis G, McIntosh ML, Nishiyama SI, Yoshimura F. Mechanism and implications of CXCR4- mediated integrin activation by Porphyromonas gingivalis. Mol Oral Microbiol 2013; 28:239-49; PMID: 23331495; http://dx.doi.org/10.1111/omi.12021
46. Hajishengallis G, Harokopakis E. Porphyromonas gingivalis interactions with complement receptor 3 (CR3): innate immunity or immune evasion? Front Biosci 2007; 12:4547-57; PMID:17485396; http://dx.doi. org/10.2741/2409
47. Kayagaki N, Wong MT, Stowe IB, Ramani SR, Gonzalez LC, Akashi-Takamura S, Miyake K, Zhang J, Lee WP, Muszynski A, et al. Noncanonical inflammasome activation by intracellular LPS independent of TLR4. Science 2013; 341:1246-9; PMID:23887873; http:// dx.doi.org/10.1126/science.1240248
48. Coats SR, Jones JW, Do CT, Braham PH, Bainbridge BW, To TT, Goodlett DR, Ernst RK, Darveau RP. Human Toll-like receptor 4 responses to P. gingivalis are regulated by lipid A 1- and 4’-phosphatase activities. Cell Microbiol 2009; 11:1587-99; PMID:19552698; http://dx.doi.org/10.1111/j.1462-5822.2009.01349.x
49. Slocum C, Coats SR, Hua N, Kramer C, Papadopoulos G, Weinberg EO, Gudino CV, Hamilton JA, Darveau RP, Genco CA. Distinct lipid A moieties contribute to pathogen-induced site-specific vascular inflammation. PLoS Pathog 2014; 10:e1004215; PMID:25010102; http://dx.doi.org/10.1371/journal.ppat.1004215
50. Lamkanfi M, Dixit VM. Mechanisms and functions of inflammasomes. Cell 2014; 157:1013-22; PMID: 24855941; http://dx.doi.org/10.1016/j.cell.2014. 04.007
51. Shi J, Zhao Y, Wang Y, Gao W, Ding J, Li P, Hu L, Shao F. Inflammatory caspases are innate immune receptors for intracellular LPS. Nature 2014; 514: 187-92; PMID:25119034; http://dx.doi.org/10.1038/ nature13820
52. Zenobia C, Luo XL, Hashim A, Abe T, Jin L, Chang Y, Jin ZC, Sun JX, Hajishengallis G, Curtis MA, et al. Commensal bacteria-dependent select expression of CXCL2 contributes to periodontal tissue homeostasis. Cell Microbiol 2013; 15:1419-26; PMID:23433011; http://dx.doi.org/10.1111/cmi.12127
53. Zenobia C, Hasturk H, Nguyen D, Van Dyke TE, Kantarci A, Darveau RP. Porphyromonas gingivalis lipid A phosphatase activity is critical for colonization and increasing the commensal load in the rabbit ligature model. Infect Immun 2014; 82:650-9; PMID: 24478080; http://dx.doi.org/10.1128/IAI.01136-13
54. Cutler CW, Jotwani R. Dendritic cells at the oral mucosal interface. J Dent Res 2006; 85:678-89; PMID:16861283; http://dx.doi.org/10.1177/1544059 10608500801
55. Zeituni AE, Jotwani R, Carrion J, Cutler CW. Targeting of DC-SIGN on human dendritic cells by minor fimbriated Porphyromonas gingivalis strains elicits a distinct effector T cell response. J Immunol 2009; 183:5694-704; PMID:19828628; http://dx.doi.org/ 10.4049/jimmunol.0901030
56. Carrion J, Scisci E, Miles B, Sabino GJ, Zeituni AE, Gu Y, Bear A, Genco CA, Brown DL, Cutler CW. Microbial carriage state of peripheral blood dendritic cells (DCs) in chronic periodontitis influences DC differentiation, atherogenic potential. J Immunol 2012; 189:3178-87; PMID:22891282; http://dx.doi.org/ 10.4049/jimmunol.1201053
57. Gemmell E, Yamazaki K, Seymour GJ. The role of T cells in periodontal disease: homeostasis and autoimmunity. Periodontol 2000 2007; 43:14-40; PMID:17214833; http://dx.doi.org/10.1111/j.1600- 0757.2006.00173.x
58. Garlet GP. Destructive and protective roles of cytokines in periodontitis: A re-appraisal from host defense and tissue destruction viewpoints. J Dent Res 2010; 89:1349-63; PMID:20739705; http://dx.doi.org/ 10.1177/0022034510376402
59. Gaffen SL, Hajishengallis G. A new inflammatory cytokine on the block: re-thinking periodontal disease and the Th1/Th2 paradigm in the context of Th17 cells and IL-17. J Dent Res 2008; 87:817-28; PMID:18719207; http://dx.doi.org/10.1177/1544059 10808700908
60. Gemmell E, Drysdale KE, Seymour GJ. Gene expression in splenic CD4 and CD8 cells from BALB/c mice immunized with Porphyromonas gingivalis. J Periodontol 2006; 77:622-33; PMID:16584343; http://dx.doi. org/10.1902/jop.2006.050211
61. Gaddis DE, Maynard CL, Weaver CT, Michalek SM, Katz J. Role of TLR2 dependent-IL-10 production in the inhibition of the initial IFN-g T cell response to Porphyromonas gingivalis. J Leukoc Biol 2012; 93: 21-31; PMID:23077245; http://dx.doi.org/10.1189/ jlb.0512220
62. Gemmell E, Yamazaki K, Seymour GJ. The role of T cells in periodontal disease: homeostasis and autoimmunity. Periodontology 2000 2007; 43:14-40; PMID: NOT_FOUND; http://dx.doi.org/10.1111/j.1600- 0757.2006.00173.x
63. Jiao Y, Hasegawa M, Inohara N. The Role of Oral Pathobionts in Dysbiosis during Periodontitis Development. J Dent Res 2014; 93:539-46; PMID:24646638; http://dx.doi.org/10.1177/0022034514528212
64. Abe T, Hosur KB, Hajishengallis E, Reis ES, Ricklin D, Lambris JD, Hajishengallis G. Local complementtargeted intervention in periodontitis: proof-of-concept using a C5a receptor (CD88) antagonist. J Immunol 2012; 189:5442-8; PMID:23089394; http://dx.doi. org/10.4049/jimmunol.1202339
65. Yilmaz O, Jungas T, Verbeke P, Ojcius DM. Activation of the phosphatidylinositol 3-kinase/Akt pathway contributes to survival of primary epithelial cells infected with the periodontal pathogen Porphyromonas gingivalis. Infect Immun 2004; 72:3743-51; PMID:15213114; http://dx.doi.org/10.1128/ IAI.72.7.3743-3751.2004
66. Darveau RP. Porphyromonas gingivalis neutrophil manipulation: risk factor for periodontitis? Trends Microbiol 2014; PMID:25001854; http://dx.doi.org/ 10.1016/j.tim.2014.06.006 (Epub ahead of print)
67. Haffajee AD, Cugini MA, Tanner A, Pollack RP, Smith C, Kent RL, Jr., Socransky SS. Subgingival microbiota in healthy, well-maintained elder and periodontitis subjects. J Clin Periodontol 1998; 25:346-53; PMID:9650869; http://dx.doi.org/10.1111/j.1600- 051X.1998.tb02454.x
68. Darveau RP, Hajishengallis G, Curtis MA. Porphyromonas gingivalis as a potential community activist for disease. J Dent Res 2012; 91:816-20; PMID: 22772362; http://dx.doi.org/10.1177/00220345 12453589
69. Laine ML, Crielaard W, Loos BG. Genetic susceptibility to periodontitis. Periodontol 2000 2012; 58:37-68; PMID:22133366; http://dx.doi.org/10.1111/j.1600- 0757.2011.00415.x
70. Socransky SS, Haffajee AD. Evidence of bacterial etiology: a historical perspective. Periodontol 2000 1994; 5:7-25; PMID:9673160; http://dx.doi.org/10.1111/ j.1600-0757.1994.tb00016.x
71. Bostanci N, Belibasakis GN. Porphyromonas gingivalis: an invasive and evasive opportunistic oral pathogen. FEMS Microbiol Lett 2012; 333:1-9; PMID:22530835; http://dx.doi.org/10.1111/j.1574- 6968.2012.02579.x
72. Barth K, Remick DG, Genco CA. Disruption of immune regulation by microbial pathogens and resulting chronic inflammation. J Cell Physiol 2013; 228:1413-22; PMID:23255141; http://dx.doi.org/ 10.1002/jcp.24299
73. Yilmaz O. The chronicles of Porphyromonas gingivalis: the microbium, the human oral epithelium and their interplay. Microbiology 2008; 154:2897-903; PMID:18832296; http://dx.doi.org/10.1099/ mic.0.2008/021220-0
74. Guo Y, Nguyen KA, Potempa J. Dichotomy of gingipains action as virulence factors: from cleaving substrates with the precision of a surgeon’s knife to a meat chopper-like brutal degradation of proteins. Periodontol 2000 2010; 54:15-44; PMID:20712631; http://dx. doi.org/10.1111/j.1600-0757.2010.00377.x
75. Bao K, Belibasakis GN, Thurnheer T, Aduse-Opoku J, Curtis MA, Bostanci N. Role of Porphyromonas gingivalis gingipains in multi-species biofilm formation. BMC Microbiol 2014; 14:258; PMID:25270662; http://dx. doi.org/10.1186/s12866-014-0258-7
76. Popadiak K, Potempa J, Riesbeck K, Blom AM. Biphasic effect of gingipains from Porphyromonas gingivalis on the human complement system. J Immunol 2007; 178:7242-50; PMID:17513773; http://dx.doi. org/10.4049/jimmunol.178.11.7242
77. Potempa M, Potempa J, Kantyka T, Nguyen KA, Wawrzonek K, Manandhar SP, Popadiak K, Riesbeck K, Eick S, Blom AM. Interpain A, a cysteine proteinase from Prevotella intermedia, inhibits complement by degrading complement factor C3. PLoS Pathog 2009; 5:e1000316; PMID:19247445; http://dx.doi.org/ 10.1371/journal.ppat.1000316
78. Nussbaum G, Shapira L. How has neutrophil research improved our understanding of periodontal pathogenesis? J Clin Periodontol 2011; 38:49-59; PMID:21323704; http://dx.doi.org/10.1111/j.1600- 051X.2010.01678.x
79. Wang M, Krauss JL, Domon H, Hosur KB, Liang S, Magotti P, Triantafilou M, Triantafilou K, Lambris JD, Hajishengallis G. Microbial hijacking of complement- toll-like receptor crosstalk. Sci Signal 2010; 3: ra11; PMID:20159852
80. Potempa M, Potempa J, Okroj M, Popadiak K, Eick S, Nguyen KA, Riesbeck K, Blom AM. Binding of complement inhibitor C4b-binding protein contributes to serum resistance of Porphyromonas gingivalis. J Immunol 2008; 181:5537-44; PMID: 18832711; http://dx.doi.org/10.4049/jimmunol. 181.8.5537
81. Mahtout H, Chandad F, Rojo JM, Grenier D. Porphyromonas gingivalis mediates the shedding and proteolysis of complement regulatory protein CD46 expressed by oral epithelial cells. Oral Microbiol Immunol 2009; 24:396-400; PMID:19702953; http://dx.doi.org/ 10.1111/j.1399-302X.2009.00532.x
82. Coats SR, Jones JW, Do CT, Braham PH, Bainbridge BW, To TT, Goodlett DR, Ernst RK, Darveau RP. Human Toll-like receptor 4 responses to P. gingivalis are regulated by lipid A 1- and 4’- phosphatase activities. Cell Microbiol 2009; 11:1587-99; PMID:19552698; http://dx.doi.org/10.1111/j.1462- 5822.2009.01349.x
83. Maresz KJ, Hellvard A, Sroka A, Adamowicz K, Bielecka E, Koziel J, Gawron K, Mizgalska D, Marcinska KA, Benedyk M, et al. Porphyromonas gingivalis facilitates the development and progression of destructive arthritis through its unique bacterial peptidylarginine deiminase (PAD). PLoS Pathog 2013; 9:e1003627; PMID:24068934; http://dx.doi.org/10.1371/journal. ppat.1003627
84. Wegner N, Wait R, Sroka A, Eick S, Nguyen KA, Lundberg K, Kinloch A, Culshaw S, Potempa J, Venables PJ. Peptidylarginine deiminase from Porphyromonas gingivalis citrullinates human fibrinogen and alphaenolase: implications for autoimmunity in rheumatoid arthritis. Arthritis Rheumatol 2010; 62:2662-72; PMID:NOT_FOUND; http://dx.doi.org/10.1002/ art.27552
85. Yilmaz O, Yao L, Maeda K, Rose TM, Lewis EL, Duman M, Lamont RJ, Ojcius DM. ATP scavenging by the intracellular pathogen Porphyromonas gingivalis inhibits P2X7-mediated host-cell apoptosis. Cell Microbiol 2008; 10:863-75; PMID:18005240; http:// dx.doi.org/10.1111/j.1462-5822.2007.01089.x
86. Choi CH, Spooner R, DeGuzman J, Koutouzis T, Ojcius DM, Yilmaz O. Porphyromonas gingivalis-nucleoside- diphosphate-kinase inhibits ATP-induced reactive- oxygen-species via P2X7 receptor/NADPHoxidase signalling and contributes to persistence. Cell Microbiol 2013; 15:961-76; PMID:23241000; http:// dx.doi.org/10.1111/cmi.12089
87. Hajishengallis G, Lambris JD. Microbial manipulation of receptor crosstalk in innate immunity. Nat Rev Immunol 2011; 11:187-200; PMID:21350579; http:// dx.doi.org/10.1038/nri2918
88. Hajishengallis G, Lamont RJ. Breaking bad: Manipulation of the host response by Porphyromonas gingivalis. Eur J Immunol 2014; 44:328-38; PMID:24338806; http://dx.doi.org/10.1002/eji.201344202
89. Zeituni AE, McCaig W, Scisci E, Thanassi DG, Cutler CW. The native 67-kilodalton minor fimbria of Porphyromonas gingivalis is a novel glycoprotein with DCSIGN- targeting motifs. J Bacteriol 2010; 192:4103-10; PMID:20562309; http://dx.doi.org/10.1128/ JB.00275-10
90. Nakayama K. Porphyromonas gingivalis cell-induced hemagglutination and platelet aggregation. Periodontol 2000 2010; 54:45-52; PMID:20712632; http://dx.doi. org/10.1111/j.1600-0757.2010.00351.x