Immune evasion strategies used by Helicobacter pylori

World Journal of Gastroenterology

Volumn 20, Issue 36, 2014, Pages 12753-12766

  Lina, Taslima T ^a   Alzahrani, Shatha ^a   Gonzalez, Jazmin ^b   Pinchuk, Irina V ^a   Beswick, Ellen J ^c   Reyes, Victor E ^b  

^a University of Texas Medical Branch School of Medicine   (United States)

^b UNIVERSITY OF TEXAS MEDICAL BRANCH   (United States)

^c UNIVERSITY OF NEW MEXICO HEALTH SCIENCES CENTER   (United States)

Author keywords

Antigen presenting cells; Gastric epithelial cells; Helicobacter pylori; Immune response; Pattern recognition receptors; Phagocytes; T cells; T4SS; Vacuolating cytotoxin

Indexed keywords

NITRIC OXIDE; PATTERN RECOGNITION RECEPTOR; REACTIVE OXYGEN METABOLITE; VIRULENCE FACTOR;

ADAPTIVE IMMUNITY; ANTIGEN PRESENTATION; ANTIGEN PRESENTING CELL; APOPTOSIS; DENDRITIC CELL; GASTRITIS; GENETIC VARIABILITY; HELICOBACTER PYLORI; HOST RESISTANCE; HUMAN; HUMORAL IMMUNITY; IMMUNE EVASION; INNATE IMMUNITY; LYMPHOCYTE PROLIFERATION; MACROPHAGE; NONHUMAN; PEPTIC ULCER; PERSISTENT INFECTION; PHAGOCYTE; REGULATORY T LYMPHOCYTE; REVIEW; SIGNAL TRANSDUCTION; STOMACH CANCER; STOMACH EPITHELIUM; STOMACH MUCOSA; STOMACH MUCUS; SURVIVAL; T LYMPHOCYTE; ANIMAL; EPITHELIUM CELL; GENETICS; GENOTYPE; HELICOBACTER INFECTIONS; IMMUNOLOGY; IMMUNOTHERAPY; METABOLISM; MICROBIAL VIABILITY; MICROBIOLOGY; MUCOSAL IMMUNITY; PATHOGENICITY; PROCEDURES; VIRULENCE;

ADAPTIVE IMMUNITY; ANIMALS; EPITHELIAL CELLS; GASTRIC MUCOSA; GENOTYPE; HELICOBACTER INFECTIONS; HELICOBACTER PYLORI; HUMANS; IMMUNE EVASION; IMMUNITY, HUMORAL; IMMUNITY, INNATE; IMMUNITY, MUCOSAL; IMMUNOTHERAPY; MICROBIAL VIABILITY; T-LYMPHOCYTES; VIRULENCE;

EID: 84928410099     PISSN: 10079327     EISSN: 22192840     Source Type: Journal    
DOI: 10.3748/wjg.v20.i36.12753     Document Type: Review

References (122)

1. Chong J, Marshall BJ, Barkin JS, McCallum RW, Reiner DK, Hoffman SR, O'Phelan C. Occupational exposure to Helicobacter pylori for the endoscopy professional: a sera epidemiological study. Am J Gastroenterol 1994; 89: 1987-1992 [PMID: 7942723]
2. Nakamura S, Yao T, Aoyagi K, Iida M, Fujishima M, Tsuneyoshi M. Helicobacter pylori and primary gastric lymphoma. A histopathologic and immunohistochemical analysis of 237 patients. Cancer 1997; 79: 3-11 [PMID: 8988720]
3. Parsonnet J, Isaacson PG. Bacterial infection and MALT lymphoma. N Engl J Med 2004; 350: 213-215 [PMID: 14724298 DOI: 10.1056/NEJMp038200]
4. Infection with Helicobacter pylori. IARC Monogr Eval Carcinog Risks Hum 1994; 61: 177-240 [PMID: 7715070]
5. Lee MS, Kim YJ. Signaling pathways downstream of pattern-recognition receptors and their cross talk. Annu Rev Biochem 2007; 76: 447-480 [PMID: 17328678 DOI: 10.1146/annurev.biochem.76.060605.122847]
6. Cullen TW, Giles DK, Wolf LN, Ecobichon C, Boneca IG, Trent MS. Helicobacter pylori versus the host: remodeling of the bacterial outer membrane is required for survival in the gastric mucosa. PLoS Pathog 2011; 7: e1002454 [PMID: 22216004 DOI: 10.1371/journal.ppat.1002454]
7. WL Structure of Bacterial Cells. In: Levinson WE, editor. Review of Medical Microbiology & Immunology. 12th ed. New York: McGraw-Hill, 2012
8. Wang G, Ge Z, Rasko DA, Taylor DE. Lewis antigens in Helicobacter pylori: biosynthesis and phase variation. Mol Microbiol 2000; 36: 1187-1196 [PMID: 10931272 DOI: 10.1046/j.1365-2958.2000.01934.x]
9. Tran AX, Stead CM, Trent MS. Remodeling of Helicobacter pylori lipopolysaccharide. J Endotoxin Res 2005; 11: 161-166 [PMID: 15949144 DOI: 10.1179/096805105X37349]
10. Moran AP. Molecular Structure, Biosynthesis, and Pathogenic Roles of Lipopolysaccharides. In: Mobley HLT MG, Hazell SL, editors. Helicobacter pylori: Physiology and Genetics. Washington (DC): ASM Press, 2001
11. Grebowska A, Moran AP, Matusiak A, Bak-Romaniszyn L, Czkwianianc E, Rechciński T, Walencka M, Płaneta-Małecka I, Rudnicka W, Chmiela M. Anti-phagocytic activity of Helicobacter pylori lipopolysaccharide (LPS) - possible modulation of the innate immune response to these bacteria. Pol J Microbiol 2008; 57: 185-192 [PMID: 19004238]
12. Brooks GF, Butel JS, Morse SA, Mietzner TA. Cell Structure. In: Brooks KCC GF, Butel JS, Morse SA, Mietzner TA, editors. Jawetz, Melnick, Adelberg's Medical Microbiology. 26th ed. New York: McGraw-Hill, 2013
13. Gewirtz AT, Yu Y, Krishna US, Israel DA, Lyons SL, Peek RM. Helicobacter pylori flagellin evades toll-like receptor 5-mediated innate immunity. J Infect Dis 2004; 189: 1914-1920 [PMID: 15122529 DOI: 10.1086/386289]
14. Andersen-Nissen E, Smith KD, Strobe KL, Barrett SL, Cookson BT, Logan SM, Aderem A. Evasion of Toll-like receptor 5 by flagellated bacteria. Proc Natl Acad Sci USA 2005; 102: 9247-9252 [PMID: 15956202 DOI: 10.1073/pnas.0502040102]
15. Appelmelk BJaV G, Christina MJE. Lipopolysaccharide Lewis Antigens. In: Mobley HLT MG, Hazell SL, editors. Helicobacter pylori: Physiology and Genetics. Washington (DC): ASM Press, 2001
16. Geijtenbeek TB, Gringhuis SI. Signalling through C-type lectin receptors: shaping immune responses. Nat Rev Immunol 2009; 9: 465-479 [PMID: 19521399 DOI: 10.1038/nri2569]
17. Miszczyk E, Rudnicka K, Moran AP, Fol M, Kowalewicz-Kulbat M, Druszczyńska M, Matusiak A, Walencka M, Rudnicka W, Chmiela M. Interaction of Helicobacter pylori with C-type lectin dendritic cell-specific ICAM grabbing nonintegrin. J Biomed Biotechnol 2012; 2012: 206463 [PMID: 22550396 DOI: 10.1155/2012/206463]
18. Bergman MP, Engering A, Smits HH, van Vliet SJ, van Bodegraven AA, Wirth HP, Kapsenberg ML, Vandenbroucke-Grauls CM, van Kooyk Y, Appelmelk BJ. Helicobacter pylori modulates the T helper cell 1/T helper cell 2 balance through phase-variable interaction between lipopolysaccharide and DC-SIGN. J Exp Med 2004; 200: 979-990 [PMID: 15492123 DOI: 10.1084/jem.20041061]
19. Telford JL, Covacci A, Rappuoli R, Chiara P. Immunobiology of Helicobacter pylori infection. Curr Opin Immunol 1997; 9: 498-503 [PMID: 9287174]
20. Ramarao N, Gray-Owen SD, Backert S, Meyer TF. Helicobacter pylori inhibits phagocytosis by professional phagocytes involving type IV secretion components. Mol Microbiol 2000; 37: 1389-1404 [PMID: 10998171]
21. Ramarao N, Meyer TF. Helicobacter pylori resists phagocytosis by macrophages: quantitative assessment by confocal microscopy and fluorescence-activated cell sorting. Infect Immun 2001; 69: 2604-2611 [PMID: 11254625 DOI: 10.1128/IAI.69.4.2604-2611.2001]
22. Allen LA, Schlesinger LS, Kang B. Virulent strains of Helicobacter pylori demonstrate delayed phagocytosis and stimulate homotypic phagosome fusion in macrophages. J Exp Med 2000; 191: 115-128 [PMID: 10620610]
23. Allen LA . Phagocytosis and persistence of Helicobacter pylori. Cell Microbiol 2007; 9: 817-828 [PMID: 17346311 DOI: 10.1111/j.1462-5822.2007.00906.x]
24. Zheng PY, Jones NL. Helicobacter pylori strains expressing the vacuolating cytotoxin interrupt phagosome maturation in macrophages by recruiting and retaining TACO (coronin 1) protein. Cell Microbiol 2003; 5: 25-40 [PMID: 12542468]
25. Rittig MG, Shaw B, Letley DP, Thomas RJ, Argent RH, Atherton JC. Helicobacter pylori-induced homotypic phagosome fusion in human monocytes is independent of the bacterial vacA and cag status. Cell Microbiol 2003; 5: 887-899 [PMID: 14641174]
26. Molinari M, Salio M, Galli C, Norais N, Rappuoli R, Lanzavecchia A, Montecucco C. Selective inhibition of Ii-dependent antigen presentation by Helicobacter pylori toxin VacA. J Exp Med 1998; 187: 135-140 [PMID: 9419220]
27. Weiss G, Forster S, Irving A, Tate M, Ferrero RL, Hertzog P, Frøkiær H, Kaparakis-Liaskos M. Helicobacter pylori VacA suppresses Lactobacillus acidophilus-induced interferon beta signaling in macrophages via alterations in the endocytic pathway. MBio 2013; 4: e00609-e00612 [PMID: 23760466 DOI: 10.1128/mBio.00609-12]
28. Evans DJ, Evans DG, Takemura T, Nakano H, Lampert HC, Graham DY, Granger DN, Kvietys PR. Characterization of a Helicobacter pylori neutrophil-activating protein. Infect Immun 1995; 63: 2213-2220 [PMID: 7768601]
29. Polenghi A, Bossi F, Fischetti F, Durigutto P, Cabrelle A, Tamassia N, Cassatella MA, Montecucco C, Tedesco F, de Bernard M. The neutrophil-activating protein of Helicobacter pylori crosses endothelia to promote neutrophil adhesion in vivo. J Immunol 2007; 178: 1312-1320 [PMID: 17237377]
30. Satin B, Del Giudice G, Della Bianca V, Dusi S, Laudanna C, Tonello F, Kelleher D, Rappuoli R, Montecucco C, Rossi F. The neutrophil-activating protein (HP-NAP) of Helicobacter pylori is a protective antigen and a major virulence factor. J Exp Med 2000; 191: 1467-1476 [PMID: 10790422]
31. Odenbreit S, Wieland B, Haas R. Cloning and genetic characterization of Helicobacter pylori catalase and construction of a catalase-deficient mutant strain. J Bacteriol 1996; 178: 6960-6967 [PMID: 8955320]
32. Spiegelhalder C, Gerstenecker B, Kersten A, Schiltz E, Kist M. Purification of Helicobacter pylori superoxide dismutase and cloning and sequencing of the gene. Infect Immun 1993; 61: 5315-5325 [PMID: 8225605]
33. Schmausser B, Josenhans C, Endrich S, Suerbaum S, Sitaru C, Andrulis M, Brändlein S, Rieckmann P, Müller-Hermelink HK, Eck M. Downregulation of CXCR1 and CXCR2 expression on human neutrophils by Helicobacter pylori: a new pathomechanism in H. pylori infection? Infect Immun 2004; 72: 6773-6779 [PMID: 15557597 DOI: 10.1128/IAI.72.12.6773-6779.2004]
34. Allen LA, Beecher BR, Lynch JT, Rohner OV, Wittine LM. Helicobacter pylori disrupts NADPH oxidase targeting in human neutrophils to induce extracellular superoxide release. J Immunol 2005; 174: 3658-3667 [PMID: 15749904]
35. Lewis ND, Asim M, Barry DP, Singh K, de Sablet T, Boucher JL, Gobert AP, Chaturvedi R, Wilson KT. Arginase II restricts host defense to Helicobacter pylori by attenuating inducible nitric oxide synthase translation in macrophages. J Immunol 2010; 184: 2572-2582 [PMID: 20097867 DOI: 10.4049/jimmunol.0902436]
36. Gobert AP, McGee DJ, Akhtar M, Mendz GL, Newton JC, Cheng Y, Mobley HL, Wilson KT. Helicobacter pylori arginase inhibits nitric oxide production by eukaryotic cells: a strategy for bacterial survival. Proc Natl Acad Sci USA 2001; 98: 13844-13849 [PMID: 11717441 DOI: 10.1073/pnas.241443798]
37. Lewis ND, Asim M, Barry DP, de Sablet T, Singh K, Piazuelo MB, Gobert AP, Chaturvedi R, Wilson KT. Immune evasion by Helicobacter pylori is mediated by induction of macrophage arginase II. J Immunol 2011; 186: 3632-3641 [PMID: 21296975 DOI: 10.4049/jimmunol.1003431]
38. Quiding-Järbrink M, Raghavan S, Sundquist M. Enhanced M1 macrophage polarization in human helicobacter pylori-associated atrophic gastritis and in vaccinated mice. PLoS One 2010; 5: e15018 [PMID: 21124899 DOI: 10.1371/journal.pone.0015018]
39. Fehlings M, Drobbe L, Moos V, Renner Viveros P, Hagen J, Beigier-Bompadre M, Pang E, Belogolova E, Churin Y, Schneider T, Meyer TF, Aebischer T, Ignatius R. Comparative analysis of the interaction of Helicobacter pylori with human dendritic cells, macrophages, and monocytes. Infect Immun 2012; 80: 2724-2734 [PMID: 22615251 DOI: 10.1128/IAI.00381-12]
40. Alvi A, Ansari SA, Ehtesham NZ, Rizwan M, Devi S, Sechi LA, Qureshi IA, Hasnain SE, Ahmed N. Concurrent proinflammatory and apoptotic activity of a Helicobacter pylori protein (HP986) points to its role in chronic persistence. PLoS One 2011; 6: e22530 [PMID: 21789261 DOI: 10.1371/journal.pone.0022530]
41. Asim M, Chaturvedi R, Hoge S, Lewis ND, Singh K, Barry DP, Algood HS, de Sablet T, Gobert AP, Wilson KT. Helicobacter pylori induces ERK-dependent formation of a phospho-c-Fos c-Jun activator protein-1 complex that causes apoptosis in macrophages. J Biol Chem 2010; 285: 20343-20357 [PMID: 20410304 DOI: 10.1074/jbc.M110.116988]
42. Cheng Y, Chaturvedi R, Asim M, Bussière FI, Scholz A, Xu H, Casero RA, Wilson KT. Helicobacter pylori-induced macrophage apoptosis requires activation of ornithine decarboxylase by c-Myc. J Biol Chem 2005; 280: 22492-22496 [PMID: 15843384 DOI: 10.1074/jbc.C500122200]
43. Luo JJ, Li CY, Liu S, Yu W, Tang SY, Cai HL, Zhang Y. Overexpression of Helicobacter pylori VacA N-terminal fragment induces proinflammatory cytokine expression and apoptosis in human monocytic cell line through activation of NF-κB. Can J Microbiol 2013; 59: 523-533 [PMID: 23898995 DOI: 10.1139/cjm-2013-0021]
44. Kim JM, Kim JS, Yoo DY, Ko SH, Kim N, Kim H, Kim YJ. Stimulation of dendritic cells with Helicobacter pylori vacuolating cytotoxin negatively regulates their maturation via the restoration of E2F1. Clin Exp Immunol 2011; 166: 34-45 [PMID: 21910723 DOI: 10.1111/j.1365-2249.2011.04447.x]
45. Tanaka H, Yoshida M, Nishiumi S, Ohnishi N, Kobayashi K, Yamamoto K, Fujita T, Hatakeyama M, Azuma T. The CagA protein of Helicobacter pylori suppresses the functions of dendritic cell in mice. Arch Biochem Biophys 2010; 498: 35-42 [PMID: 20363211 DOI: 10.1016/j.abb.2010.03.021]
46. Mitchell P, Germain C, Fiori PL, Khamri W, Foster GR, Ghosh S, Lechler RI, Bamford KB, Lombardi G. Chronic exposure to Helicobacter pylori impairs dendritic cell function and inhibits Th1 development. Infect Immun 2007; 75: 810-819 [PMID: 17101659 DOI: 10.1128/IAI.00228-06]
47. Wang YH, Gorvel JP, Chu YT, Wu JJ, Lei HY. Helicobacter pylori impairs murine dendritic cell responses to infection. PLoS One 2010; 5: e10844 [PMID: 20523725 DOI: 10.1371/journal.pone.0010844]
48. Oertli M, Sundquist M, Hitzler I, Engler DB, Arnold IC, Reuter S, Maxeiner J, Hansson M, Taube C, Quiding-Järbrink M, Müller A. DC-derived IL-18 drives Treg differentiation, murine Helicobacter pylori-specific immune tolerance, and asthma protection. J Clin Invest 2012; 122: 1082-1096 [PMID: 22307326 DOI: 10.1172/JCI61029]
49. Reyes VE, Lu S, Humphreys RE. Cathepsin B cleavage of Ii from class II MHC alpha- and beta-chains. J Immunol 1991; 146: 3877-3880 [PMID: 2033257]
50. Pierre P, Mellman I. Developmental regulation of invariant chain proteolysis controls MHC class II trafficking in mouse dendritic cells. Cell 1998; 93: 1135-1145 [PMID: 9657147 DOI: 10.1016/S0092-8674(00)81458-0]
51. Xu M, Capraro GA, Daibata M, Reyes VE, Humphreys RE. Cathepsin B cleavage and release of invariant chain from MHC class II molecules follow a staged pattern. Mol Immunol 1994; 31: 723-731 [PMID: 8035834]
52. Ishii N, Chiba M, Iizuka M, Watanabe H, Ishioka T, Masamune O. Expression of MHC class II antigens (HLA-DR, -DP, and -DQ) on human gastric epithelium. Gastroenterol Jpn 1992; 27: 23-28 [PMID: 1555745]
53. Ye G, Barrera C, Fan X, Gourley WK, Crowe SE, Ernst PB, Reyes VE. Expression of B7-1 and B7-2 costimulatory molecules by human gastric epithelial cells: potential role in CD4+ T cell activation during Helicobacter pylori infection. J Clin Invest 1997; 99: 1628-1636 [PMID: 9120006 DOI: 10.1172/JCI119325]
54. Jones NL, Day AS, Jennings HA, Sherman PM. Helicobacter pylori induces gastric epithelial cell apoptosis in association with increased Fas receptor expression. Infect Immun 1999; 67: 4237-4242 [PMID: 10417197]
55. Ding SZ, Minohara Y, Fan XJ, Wang J, Reyes VE, Patel J, Dirden-Kramer B, Boldogh I, Ernst PB, Crowe SE. Helicobacter pylori infection induces oxidative stress and programmed cell death in human gastric epithelial cells. Infect Immun 2007; 75: 4030-4039 [PMID: 17562777 DOI: 10.1128/IAI.00172-07]
56. Fan X, Gunasena H, Cheng Z, Espejo R, Crowe SE, Ernst PB, Reyes VE. Helicobacter pylori urease binds to class II MHC on gastric epithelial cells and induces their apoptosis. J Immunol 2000; 165: 1918-1924 [PMID: 10925273]
57. Cover TL, Krishna US, Israel DA, Peek RM. Induction of gastric epithelial cell apoptosis by Helicobacter pylori vacuolating cytotoxin. Cancer Res 2003; 63: 951-957 [PMID: 12615708]
58. Jain P, Luo ZQ, Blanke SR. Helicobacter pylori vacuolating cytotoxin A (VacA) engages the mitochondrial fission machinery to induce host cell death. Proc Natl Acad Sci USA 2011; 108: 16032-16037 [PMID: 21903925 DOI: 10.1073/pnas.1105175108]
59. Amarnath S, Mangus CW, Wang JC, Wei F, He A, Kapoor V, Foley JE, Massey PR, Felizardo TC, Riley JL, Levine BL, June CH, Medin JA, Fowler DH. The PDL1-PD1 axis converts human TH1 cells into regulatory T cells. Sci Transl Med 2011; 3: 111ra120 [PMID: 22133721 DOI: 10.1126/scitranslmed.3003130]
60. Bauquet AT, Jin H, Paterson AM, Mitsdoerffer M, Ho IC, Sharpe AH, Kuchroo VK. The costimulatory molecule ICOS regulates the expression of c-Maf and IL-21 in the development of follicular T helper cells and TH-17 cells. Nat Immunol 2009; 10: 167-175 [PMID: 19098919 DOI: 10.1038/ni.1690]
61. Paulos CM, Carpenito C, Plesa G, Suhoski MM, Varela-Rohena A, Golovina TN, Carroll RG, Riley JL, June CH. The inducible costimulator (ICOS) is critical for the development of human T(H)17 cells. Sci Transl Med 2010; 2: 55ra78 [PMID: 20980695 DOI: 10.1126/scitranslmed.3000448]
62. Das S, Suarez G, Beswick EJ, Sierra JC, Graham DY, Reyes VE. Expression of B7-H1 on gastric epithelial cells: its potential role in regulating T cells during Helicobacter pylori infection. J Immunol 2006; 176: 3000-3009 [PMID: 16493058]
63. Beswick EJ, Pinchuk IV, Das S, Powell DW, Reyes VE. Expression of the programmed death ligand 1, B7-H1, on gastric epithelial cells after Helicobacter pylori exposure promotes development of CD4+ CD25+ FoxP3+ regulatory T cells. Infect Immun 2007; 75: 4334-4341 [PMID: 17562772 DOI: 10.1128/IAI.00553-07]
64. Wu YY, Lin CW, Cheng KS, Lin C, Wang YM, Lin IT, Chou YH, Hsu PN. Increased programmed death-ligand-1 expression in human gastric epithelial cells in Helicobacter pylori infection. Clin Exp Immunol 2010; 161: 551-559 [PMID: 20646001 DOI: 10.1111/j.1365-2249.2010.04217.x]
65. Lina TT, Pinchuk IV, House J, Yamaoka Y, Graham DY, Beswick EJ, Reyes VE. CagA-dependent downregulation of B7-H2 expression on gastric mucosa and inhibition of Th17 responses during Helicobacter pylori infection. J Immunol 2013; 191: 3838-3846 [PMID: 23997227 DOI: 10.4049/jimmunol.1300524]
66. D'Elios MM, Manghetti M, De Carli M, Costa F, Baldari CT, Burroni D, Telford JL, Romagnani S, Del Prete G. T helper 1 effector cells specific for Helicobacter pylori in the gastric antrum of patients with peptic ulcer disease. J Immunol 1997; 158: 962-967 [PMID: 8993017]
67. Bamford KB, Fan X, Crowe SE, Leary JF, Gourley WK, Luthra GK, Brooks EG, Graham DY, Reyes VE, Ernst PB. Lymphocytes in the human gastric mucosa during Helicobacter pylori have a T helper cell 1 phenotype. Gastroenterology 1998; 114: 482-492 [PMID: 9496938 DOI: 10.1016/S0016-5085(98)70531-1]
68. Enarsson K, Lundgren A, Kindlund B, Hermansson M, Roncador G, Banham AH, Lundin BS, Quiding-Järbrink M. Function and recruitment of mucosal regulatory T cells in human chronic Helicobacter pylori infection and gastric adenocarcinoma. Clin Immunol 2006; 121: 358-368 [PMID: 16934529 DOI: 10.1016/j.clim.2006.07.002]
69. Lundgren A, Strömberg E, Sjöling A, Lindholm C, Enarsson K, Edebo A, Johnsson E, Suri-Payer E, Larsson P, Rudin A, Svennerholm AM, Lundin BS. Mucosal FOXP3-expressing CD4+ CD25high regulatory T cells in Helicobacter pylori-infected patients. Infect Immun 2005; 73: 523-531 [PMID: 15618192 DOI: 10.1128/IAI.73.1.523-531.2005]
70. Shi Y, Liu XF, Zhuang Y, Zhang JY, Liu T, Yin Z, Wu C, Mao XH, Jia KR, Wang FJ, Guo H, Flavell RA, Zhao Z, Liu KY, Xiao B, Guo Y, Zhang WJ, Zhou WY, Guo G, Zou QM. Helicobacter pylori-induced Th17 responses modulate Th1 cell responses, benefit bacterial growth, and contribute to pathology in mice. J Immunol 2010; 184: 5121-5129 [PMID: 20351183 DOI: 10.4049/jimmunol.0901115]
71. Serelli-Lee V, Ling KL, Ho C, Yeong LH, Lim GK, Ho B, Wong SB. Persistent Helicobacter pylori specific Th17 responses in patients with past H. pylori infection are associated with elevated gastric mucosal IL-1β. PLoS One 2012; 7: e39199 [PMID: 22761739 DOI: 10.1371/journal.pone.0039199]
72. Amedei A, Cappon A, Codolo G, Cabrelle A, Polenghi A, Benagiano M, Tasca E, Azzurri A, D'Elios MM, Del Prete G, de Bernard M. The neutrophil-activating protein of Helicobacter pylori promotes Th1 immune responses. J Clin Invest 2006; 116: 1092-1101 [PMID: 16543949 DOI: 10.1172/JCI27177]
73. Karttunen R, Karttunen T, Ekre HP, MacDonald TT. Interferon gamma and interleukin 4 secreting cells in the gastric antrum in Helicobacter pylori positive and negative gastritis. Gut 1995; 36: 341-345 [PMID: 7698689]
74. Kabir S. The role of interleukin-17 in the Helicobacter pylori induced infection and immunity. Helicobacter 2011; 16: 1-8 [PMID: 21241406 DOI: 10.1111/j.1523-5378.2010.00812.x]
75. DeLyria ES, Redline RW, Blanchard TG. Vaccination of mice against H pylori induces a strong Th-17 response and immunity that is neutrophil dependent. Gastroenterology 2009; 136: 247-256 [PMID: 18948106 DOI: 10.1053/j.gastro.2008.09.017]
76. Fan XJ, Chua A, Shahi CN, McDevitt J, Keeling PW, Kelleher D. Gastric T lymphocyte responses to Helicobacter pylori in patients with H pylori colonisation. Gut 1994; 35: 1379-1384 [PMID: 7959191]
77. Boncristiano M, Paccani SR, Barone S, Ulivieri C, Patrussi L, Ilver D, Amedei A, D'Elios MM, Telford JL, Baldari CT. The Helicobacter pylori vacuolating toxin inhibits T cell activation by two independent mechanisms. J Exp Med 2003; 198: 1887-1897 [PMID: 14676300 DOI: 10.1084/jem.20030621]
78. Ganten TM, Aravena E, Sykora J, Koschny R, Mohr J, Rudi J, Stremmel W, Walczak H. Helicobacter pylori-induced apoptosis in T cells is mediated by the mitochondrial pathway independent of death receptors. Eur J Clin Invest 2007; 37: 117-125 [PMID: 17217377 DOI: 10.1111/j.1365-2362.2007.01761.x]
79. Schmees C, Prinz C, Treptau T, Rad R, Hengst L, Voland P, Bauer S, Brenner L, Schmid RM, Gerhard M. Inhibition of T-cell proliferation by Helicobacter pylori gamma-glutamyl transpeptidase. Gastroenterology 2007; 132: 1820-1833 [PMID: 17484877 DOI: 10.1053/j.gastro.2007.02.031]
80. Sundrud MS, Torres VJ, Unutmaz D, Cover TL. Inhibition of primary human T cell proliferation by Helicobacter pylori vacuolating toxin (VacA) is independent of VacA effects on IL-2 secretion. Proc Natl Acad Sci USA 2004; 101: 7727-7732 [PMID: 15128946 DOI: 10.1073/pnas.0401528101]
81. Torres VJ, VanCompernolle SE, Sundrud MS, Unutmaz D, Cover TL. Helicobacter pylori vacuolating cytotoxin inhibits activation-induced proliferation of human T and B lymphocyte subsets. J Immunol 2007; 179: 5433-5440 [PMID: 17911630]
82. Wang J, Brooks EG, Bamford KB, Denning TL, Pappo J, Ernst PB. Negative selection of T cells by Helicobacter pylori as a model for bacterial strain selection by immune evasion. J Immunol 2001; 167: 926-934 [PMID: 11441100]
83. Sewald X, Gebert-Vogl B, Prassl S, Barwig I, Weiss E, Fabbri M, Osicka R, Schiemann M, Busch DH, Semmrich M, Holzmann B, Sebo P, Haas R. Integrin subunit CD18 Is the T-lymphocyte receptor for the Helicobacter pylori vacuolating cytotoxin. Cell Host Microbe 2008; 3: 20-29 [PMID: 18191791 DOI: 10.1016/j.chom.2007.11.003]
84. Gebert B, Fischer W, Weiss E, Hoffmann R, Haas R. Helicobacter pylori vacuolating cytotoxin inhibits T lymphocyte activation. Science 2003; 301: 1099-1102 [PMID: 12934009 DOI: 10.1126/science.1086871]
85. Zabaleta J, McGee DJ, Zea AH, Hernández CP, Rodriguez PC, Sierra RA, Correa P, Ochoa AC. Helicobacter pylori arginase inhibits T cell proliferation and reduces the expression of the TCR zeta-chain (CD3zeta). J Immunol 2004; 173: 586-593 [PMID: 15210820]
86. Lundgren A, Suri-Payer E, Enarsson K, Svennerholm AM, Lundin BS. Helicobacter pylori-specific CD4+ CD25high regulatory T cells suppress memory T-cell responses to H. pylori in infected individuals. Infect Immun 2003; 71: 1755-1762 [PMID: 12654789]
87. Cheng HH, Tseng GY, Yang HB, Wang HJ, Lin HJ, Wang WC. Increased numbers of Foxp3-positive regulatory T cells in gastritis, peptic ulcer and gastric adenocarcinoma. World J Gastroenterol 2012; 18: 34-43 [PMID: 22228968 DOI: 10.3748/wjg.v18.i1.34]
88. Harris PR, Wright SW, Serrano C, Riera F, Duarte I, Torres J, Peña A, Rollán A, Viviani P, Guiraldes E, Schmitz JM, Lorenz RG, Novak L, Smythies LE, Smith PD. Helicobacter pylori gastritis in children is associated with a regulatory T-cell response. Gastroenterology 2008; 134: 491-499 [PMID: 18242215 DOI: 10.1053/j.gastro.2007.11.006]
89. Arnold IC, Lee JY, Amieva MR, Roers A, Flavell RA, Sparwasser T, Müller A. Tolerance rather than immunity protects from Helicobacter pylori-induced gastric preneoplasia. Gastroenterology 2011; 140: 199-209 [PMID: 20600031 DOI: 10.1053/j.gastro.2010.06.047]
90. Flach CF, Östberg AK, Nilsson AT, Malefyt Rde W, Raghavan S. Proinflammatory cytokine gene expression in the stomach correlates with vaccine-induced protection against Helicobacter pylori infection in mice: an important role for interleukin-17 during the effector phase. Infect Immun 2011; 79: 879-886 [PMID: 21078851 DOI: 10.1128/IAI.00756-10]
91. Velin D, Favre L, Bernasconi E, Bachmann D, Pythoud C, Saiji E, Bouzourene H, Michetti P. Interleukin-17 is a critical mediator of vaccine-induced reduction of Helicobacter infection in the mouse model. Gastroenterology 2009; 136: 2237-2246.e1 [PMID: 19272385 DOI: 10.1053/j.gastro.2009.02.077]
92. Kao JY, Rathinavelu S, Eaton KA, Bai L, Zavros Y, Takami M, Pierzchala A, Merchant JL. Helicobacter pylori-secreted factors inhibit dendritic cell IL-12 secretion: a mechanism of ineffective host defense. Am J Physiol Gastrointest Liver Physiol 2006; 291: G73-G81 [PMID: 16469828 DOI: 10.1152/ajpgi.00139.2005]
93. Kao JY, Zhang M, Miller MJ, Mills JC, Wang B, Liu M, Eaton KA, Zou W, Berndt BE, Cole TS, Takeuchi T, Owyang SY, Luther J. Helicobacter pylori immune escape is mediated by dendritic cell-induced Treg skewing and Th17 suppression in mice. Gastroenterology 2010; 138: 1046-1054 [PMID: 19931266 DOI: 10.1053/j.gastro.2009.11.043]
94. Lin R, Ma H, Ding Z, Shi W, Qian W, Song J, Hou X. Bone marrow-derived mesenchymal stem cells favor the immunosuppressive T cells skewing in a Helicobacter pylori model of gastric cancer. Stem Cells Dev 2013; 22: 2836-2848 [PMID: 23777268 DOI: 10.1089/scd.2013.0166]
95. Soares TF, Rocha GA, Rocha AM, Corrêa-Oliveira R, Martins-Filho OA, Carvalho AS, Bittencourt P, Oliveira CA, Faria AM, Queiroz DM. Phenotypic study of peripheral blood lymphocytes and humoral immune response in Helicobacter pylori infection according to age. Scand J Immunol 2005; 62: 63-70 [PMID: 16091125 DOI: 10.1111/j.1365-3083.2005.01638.x]
96. Manojlovic N, Nikolic L, Pilcevic D, Josifovski J, Babic D. Systemic humoral anti-Helicobacter pylori immune response in patients with gastric malignancies and benign gastroduodenal disease. Hepatogastroenterology 2004; 51: 282-284 [PMID: 15011886]
97. Yamaji Y, Mitsushima T, Ikuma H, Okamoto M, Yoshida H, Kawabe T, Shiratori Y, Saito K, Yokouchi K, Omata M. Weak response of helicobacter pylori antibody is high risk for gastric cancer: a cross-sectional study of 10,234 endoscoped Japanese. Scand J Gastroenterol 2002; 37: 148-153 [PMID: 11843049]
98. Iaquinto G, Todisco A, Giardullo N, D'Onofrio V, Pasquale L, De Luca A, Andriulli A, Perri F, Rega C, De Chiara G, Landi M, Taccone W, Leandro G, Figura N. Antibody response to Helicobacter pylori CagA and heat-shock proteins in determining the risk of gastric cancer development. Dig Liver Dis 2000; 32: 378-383 [PMID: 11030181 DOI: 10.1016/S1590-8658(00)80256-X]
99. Ermak TH, Giannasca PJ, Nichols R, Myers GA, Nedrud J, Weltzin R, Lee CK, Kleanthous H, Monath TP. Immunization of mice with urease vaccine affords protection against Helicobacter pylori infection in the absence of antibodies and is mediated by MHC class II-restricted responses. J Exp Med 1998; 188: 2277-2288 [PMID: 9858514]
100. Akhiani AA, Schön K, Franzén LE, Pappo J, Lycke N. Helicobacter pylori-specific antibodies impair the development of gastritis, facilitate bacterial colonization, and counteract resistance against infection. J Immunol 2004; 172: 5024-5033 [PMID: 15067084]
101. Darwin PE, Sztein MB, Zheng QX, James SP, Fantry GT. Immune evasion by Helicobacter pylori: gastric spiral bacteria lack surface immunoglobulin deposition and reactivity with homologous antibodies. Helicobacter 1996; 1: 20-27 [PMID: 9398909]
102. Basso D, Gallo N, Zambon CF, Baron M, Navaglia F, Stockreiter E, Di Mario F, Rugge M, Plebani M. Antigastric autoantibodies in Helicobacter pylori infection: role in gastric mucosal inflammation. Int J Clin Lab Res 2000; 30: 173-178 [PMID: 11289707]
103. Faller G, Ruff S, Reiche N, Hochberger J, Hahn EG, Kirchner T. Mucosal production of antigastric autoantibodies in Helicobacter pylori gastritis. Helicobacter 2000; 5: 129-134 [PMID: 10971676 DOI: 10.1046/j.1523-5378.2000.00020.x]
104. Parente F, Negrini R, Imbesi V, Maconi G, Sainaghi M, Vago L, Bianchi Porro G. Presence of gastric autoantibodies impairs gastric secretory function in patients with Helicobacter pylori-positive duodenal ulcer. Scand J Gastroenterol 2001; 36: 474-478 [PMID: 11346199]
105. Hensel F, Knörr C, Hermann R, Krenn V, Müller-Hermelink HK, Vollmers HP. Mitogenic autoantibodies in Helicobacter pylori-associated stomach cancerogenesis. Int J Cancer 1999; 81: 229-235 [PMID: 10188724 DOI: 10.1002/(SICI)1097-0215(19990412)81]
106. Alm RA, Ling LS, Moir DT, King BL, Brown ED, Doig PC, Smith DR, Noonan B, Guild BC, deJonge BL, Carmel G, Tummino PJ, Caruso A, Uria-Nickelsen M, Mills DM, Ives C, Gibson R, Merberg D, Mills SD, Jiang Q, Taylor DE, Vovis GF, Trust TJ. Genomic-sequence comparison of two unrelated isolates of the human gastric pathogen Helicobacter pylori. Nature 1999; 397: 176-180 [PMID: 9923682 DOI: 10.1038/16495]
107. Björkholm B, Sjölund M, Falk PG, Berg OG, Engstrand L, Andersson DI. Mutation frequency and biological cost of antibiotic resistance in Helicobacter pylori. Proc Natl Acad Sci USA 2001; 98: 14607-14612 [PMID: 11717398 DOI: 10.1073/pnas.241517298]
108. Suerbaum S, Smith JM, Bapumia K, Morelli G, Smith NH, Kunstmann E, Dyrek I, Achtman M. Free recombination within Helicobacter pylori. Proc Natl Acad Sci USA 1998; 95: 12619-12624 [PMID: 9770535]
109. Gressmann H, Linz B, Ghai R, Pleissner KP, Schlapbach R, Yamaoka Y, Kraft C, Suerbaum S, Meyer TF, Achtman M. Gain and loss of multiple genes during the evolution of Helicobacter pylori. PLoS Genet 2005; 1: e43 [PMID: 16217547 DOI: 10.1371/journal.pgen.0010043]
110. Higashi H, Tsutsumi R, Muto S, Sugiyama T, Azuma T, Asaka M, Hatakeyama M. SHP-2 tyrosine phosphatase as an intracellular target of Helicobacter pylori CagA protein. Science 2002; 295: 683-686 [PMID: 11743164 DOI: 10.1126/science.1067147]
111. Naito M, Yamazaki T, Tsutsumi R, Higashi H, Onoe K, Yamazaki S, Azuma T, Hatakeyama M. Influence of EPIYA-repeat polymorphism on the phosphorylation-dependent biological activity of Helicobacter pylori CagA. Gastroenterology 2006; 130: 1181-1190 [PMID: 16618412 DOI: 10.1053/j.gastro.2005.12.038]
112. Barrozo RM, Cooke CL, Hansen LM, Lam AM, Gaddy JA, Johnson EM, Cariaga TA, Suarez G, Peek RM, Cover TL, Solnick JV. Functional plasticity in the type IV secretion system of Helicobacter pylori. PLoS Pathog 2013; 9: e1003189 [PMID: 23468628 DOI: 10.1371/journal.ppat.1003189]
113. Brahmer JR, Tykodi SS, Chow LQ, Hwu WJ, Topalian SL, Hwu P, Drake CG, Camacho LH, Kauh J, Odunsi K, Pitot HC, Hamid O, Bhatia S, Martins R, Eaton K, Chen S, Salay TM, Alaparthy S, Grosso JF, Korman AJ, Parker SM, Agrawal S, Goldberg SM, Pardoll DM, Gupta A, Wigginton JM. Safety and activity of anti-PD-L1 antibody in patients with advanced cancer. N Engl J Med 2012; 366: 2455-2465 [PMID: 22658128 DOI: 10.1056/NEJMoa1200694]
114. Hamid O, Robert C, Daud A, Hodi FS, Hwu WJ, Kefford R, Wolchok JD, Hersey P, Joseph RW, Weber JS, Dronca R, Gangadhar TC, Patnaik A, Zarour H, Joshua AM, Gergich K, Elassaiss-Schaap J, Algazi A, Mateus C, Boasberg P, Tumeh PC, Chmielowski B, Ebbinghaus SW, Li XN, Kang SP, Ribas A. Safety and tumor responses with lambrolizumab (anti- PD-1) in melanoma. N Engl J Med 2013; 369: 134-144 [PMID: 23724846 DOI: 10.1056/NEJMoa1305133]
115. Topalian SL, Hodi FS, Brahmer JR, Gettinger SN, Smith DC, McDermott DF, Powderly JD, Carvajal RD, Sosman JA, Atkins MB, Leming PD, Spigel DR, Antonia SJ, Horn L, Drake CG, Pardoll DM, Chen L, Sharfman WH, Anders RA, Taube JM, McMiller TL, Xu H, Korman AJ, Jure-Kunkel M, Agrawal S, McDonald D, Kollia GD, Gupta A, Wigginton JM, Sznol M. Safety, activity, and immune correlates of anti-PD-1 antibody in cancer. N Engl J Med 2012; 366: 2443-2454 [PMID: 22658127 DOI: 10.1056/NEJMoa1200690]
116. Seto B . Rapamycin and mTOR: a serendipitous discovery and implications for breast cancer. Clin Transl Med 2012; 1: 29 [PMID: 23369283 DOI: 10.1186/2001-1326-1-29]
117. Codolo G, Fassan M, Munari F, Volpe A, Bassi P, Rugge M, Pagano F, D'Elios MM, de Bernard M. HP-NAP inhibits the growth of bladder cancer in mice by activating a cytotoxic Th1 response. Cancer Immunol Immunother 2012; 61: 31-40 [PMID: 21833592 DOI: 10.1007/s00262-011-1087-2]
118. Codolo G, Mazzi P, Amedei A, Del Prete G, Berton G, D'Elios MM, de Bernard M. The neutrophil-activating protein of Helicobacter pylori down-modulates Th2 inflammation in ovalbumin-induced allergic asthma. Cell Microbiol 2008; 10: 2355-2363 [PMID: 18671823 DOI: 10.1111/j.1462-5822.2008.01217.x]
119. Del Prete G, Chiumiento L, Amedei A, Piazza M, D'Elios MM, Codolo G, de Bernard M, Masetti M, Bruschi F. Immunosuppression of TH2 responses in Trichinella spiralis infection by Helicobacter pylori neutrophil-activating protein. J Allergy Clin Immunol 2008; 122: 908-913.e5 [PMID: 18804852 DOI: 10.1016/j.jaci.2008.08.016]
120. Moodley Y, Linz B, Yamaoka Y, Windsor HM, Breurec S, Wu JY, Maady A, Bernhöft S, Thiberge JM, Phuanukoonnon S, Jobb G, Siba P, Graham DY, Marshall BJ, Achtman M. The peopling of the Pacific from a bacterial perspective. Science 2009; 323: 527-530 [PMID: 19164753 DOI: 10.1126/science.1166083]
121. Beswick EJ, Bland DA, Suarez G, Barrera CA, Fan X, Reyes VE. Helicobacter pylori binds to CD74 on gastric epithelial cells and stimulates interleukin-8 production. Infect Immun 2005; 73: 2736-2743 [PMID: 15845476 DOI: 10.1128/IAI.73.5.2736-2743.2005]
122. Beswick EJ, Das S, Pinchuk IV, Adegboyega P, Suarez G, Yamaoka Y, Reyes VE. Helicobacter pylori-induced IL-8 production by gastric epithelial cells up-regulates CD74 expression. J Immunol 2005; 175: 171-176 [PMID: 15972644 DOI: 10.4049/jimmunol.175.1.171]