Host-bacterial interactions in Helicobacter pylori infection.

Helicobacter pylori are spiral-shaped gram-negative bacteria with polar flagella that live near the surface of the human gastric mucosa. They have evolved intricate mechanisms to avoid the bactericidal acid in the gastric lumen and to survive near, to attach to, and to communicate with the human gastric epithelium and host immune system. This interaction sometimes results in severe gastric pathology. H pylori infection is the strongest known risk factor for the development of gastroduodenal ulcers, with infection being present in 60%-80% of gastric and 95% of duodenal ulcers.(1)H pylori is also the first bacterium to be classified as a definite carcinogen by the World Health Organization's International Agency for Research on Cancer because of its epidemiologic relationship to gastric adenocarcinoma and gastric mucosa-associated lymphoid tissue lymphoma.(2) In the last 25 years, since H pylori was first described and cultured, a complete paradigm shift has occurred in our clinical approach to these gastric diseases, and more than 20,000 scientific publications have appeared on the subject. From the medical point of view, H pylori is a formidable pathogen responsible for much morbidity and mortality worldwide. However, H pylori infection occurs in approximately half of the world population, with disease being an exception rather than the rule. Understanding how this organism interacts with its host is essential for formulating an intelligent strategy for dealing with its most important clinical consequences. This review offers an insight into H pylori host-bacterial interactions.

[1]  E. Brooks,et al.  Lymphocytes in the human gastric mucosa during Helicobacter pylori have a T helper cell 1 phenotype. , 1998, Gastroenterology.

[2]  S. Falkow,et al.  Disruption of the Epithelial Apical-Junctional Complex by Helicobacter pylori CagA , 2003, Science.

[3]  R. Peek,et al.  The Role of Decay-accelerating Factor as a Receptor for Helicobacter pylori and a Mediator of Gastric Inflammation*♦ , 2006, Journal of Biological Chemistry.

[4]  D. Schwartz,et al.  TLR4 mutations are associated with endotoxin hyporesponsiveness in humans , 2000, Nature Genetics.

[5]  F. Bagnoli,et al.  Helicobacter pylori CagA induces a transition from polarized to invasive phenotypes in MDCK cells. , 2005, Proceedings of the National Academy of Sciences of the United States of America.

[6]  M. Blaser,et al.  Divergence of genetic sequences for the vacuolating cytotoxin among Helicobacter pylori strains. , 1994, The Journal of biological chemistry.

[7]  C. Prinz,et al.  Synergistic effect of Helicobacter pylori virulence factors and interleukin-1 polymorphisms for the development of severe histological changes in the gastric mucosa. , 2003, The Journal of infectious diseases.

[8]  R. Fiocca,et al.  Intracellular, intercellular, and stromal invasion of gastric mucosa, preneoplastic lesions, and cancer by Helicobacter pylori. , 2007, Gastroenterology.

[9]  M. Blaser,et al.  Helicobacter pylori cagA+ strains and dissociation of gastric epithelial cell proliferation from apoptosis. , 1997, Journal of the National Cancer Institute.

[10]  T. Koike,et al.  The polymorphism interleukin 8 −251 A/T influences the susceptibility of Helicobacter pylori related gastric diseases in the Japanese population , 2005, Gut.

[11]  T. Haggerty,et al.  Gastroenteritis and Transmission of Helicobacter pylori Infection in Households , 2006, Emerging infectious diseases.

[12]  S. Falkow,et al.  Helicobacter pylori enter and survive within multivesicular vacuoles of epithelial cells , 2002, Cellular microbiology.

[13]  P. Jansson,et al.  Phenotypic variation in molecular mimicry between Helicobacter pylori lipopolysaccharides and human gastric epithelial cell surface glycoforms. Acid-induced phase variation in Lewis(x) and Lewis(y) expression by H. Pylori lipopolysaccharides. , 2002, The Journal of biological chemistry.

[14]  K. Van Steen,et al.  Deficient host-bacteria interactions in inflammatory bowel disease? The toll-like receptor (TLR)-4 Asp299gly polymorphism is associated with Crohn’s disease and ulcerative colitis , 2004, Gut.

[15]  M. Selbach,et al.  Phosphorylation of tyrosine 972 of the Helicobacter pylori CagA protein is essential for induction of a scattering phenotype in gastric epithelial cells , 2001, Molecular microbiology.

[16]  S. Akira,et al.  Toll-like receptors in innate immunity. , 2004, International immunology.

[17]  H. Brenner,et al.  The Mother as Source of Helicobacter pylori Infection , 2006, Epidemiology.

[18]  C. Prinz,et al.  Key importance of the Helicobacter pylori adherence factor blood group antigen binding adhesin during chronic gastric inflammation. , 2001, Cancer research.

[19]  G. Tytgat Endoscopic transmission of Helicobacter pylori. , 1995, Alimentary pharmacology & therapeutics.

[20]  A. Axon,et al.  Bacterial adhesion and disease activity in Helicobacter associated chronic gastritis. , 1990, Gut.

[21]  T. Azuma,et al.  The CagA protein of Helicobacter pylori is translocated into epithelial cells and binds to SHP-2 in human gastric mucosa. , 2003, The Journal of infectious diseases.

[22]  M. Blaser,et al.  Mechanisms for Helicobacter pylori CagA‐induced cyclin D1 expression that affect cell cycle , 2006, Cellular microbiology.

[23]  H. Huynh,et al.  Helicobacter pylori Activates Toll-Like Receptor 4 Expression in Gastrointestinal Epithelial Cells , 2003, Infection and Immunity.

[24]  B. Appelmelk,et al.  Why Helicobacter pylori has Lewis antigens. , 2000, Trends in microbiology.

[25]  R. Caprioli,et al.  Carboxy-Terminal Proteolytic Processing ofHelicobacter pylori Vacuolating Toxin , 2001, Infection and Immunity.

[26]  L. Munson,et al.  Comparison of Helicobacter spp. in Cheetahs (Acinonyx jubatus) with and without Gastritis , 2005, Journal of Clinical Microbiology.

[27]  D. Czajkowsky,et al.  VacA from Helicobacter pylori: a hexameric chloride channel , 1999, FEBS letters.

[28]  L. Engstrand,et al.  Helicobacter pylori adhesin binding fucosylated histo-blood group antigens revealed by retagging. , 1998, Science.

[29]  P. Pharoah,et al.  Interleukin 1B and interleukin 1RN polymorphisms are associated with increased risk of gastric carcinoma. , 2001, Gastroenterology.

[30]  K. Magnusson,et al.  Helicobacter pylori SabA adhesin evokes a strong inflammatory response in human neutrophils which is down-regulated by the neutrophil-activating protein , 2006, Medical Microbiology and Immunology.

[31]  K. Mills,et al.  Toll-Like Receptor 4-Mediated Innate IL-10 Activates Antigen-Specific Regulatory T Cells and Confers Resistance to Bordetella pertussis by Inhibiting Inflammatory Pathology 1 , 2003, The Journal of Immunology.

[32]  S. Blanke,et al.  Helicobacter pylori vacuolating cytotoxin enters cells, localizes to the mitochondria, and induces mitochondrial membrane permeability changes correlated to toxin channel activity , 2004, Cellular microbiology.

[33]  S. Curley,et al.  Association of gastric adenocarcinoma with the HLA class II gene DQB10301. , 1996, Gastroenterology.

[34]  E. El-Omar,et al.  Interleukin 1beta polymorphisms increase risk of hypochlorhydria and atrophic gastritis and reduce risk of duodenal ulcer recurrence in Japan. , 2002, Gastroenterology.

[35]  C. Prinz,et al.  Helicobacter pylori outer membrane proteins and gastric inflammation. , 2006, Gut.

[36]  S. Falkow,et al.  Cag pathogenicity island-specific responses of gastric epithelial cells to Helicobacter pylori infection , 2002, Proceedings of the National Academy of Sciences of the United States of America.

[37]  R. Rappuoli,et al.  Selective increase of the permeability of polarized epithelial cell monolayers by Helicobacter pylori vacuolating toxin. , 1998, The Journal of clinical investigation.

[38]  D. Lin,et al.  Genetic polymorphisms of interleukin (IL)-1B, IL-1RN, IL-8, IL-10 and tumor necrosis factor {alpha} and risk of gastric cancer in a Chinese population. , 2005, Carcinogenesis.

[39]  Induction and evasion of host defenses by type 1-piliated uropathogenic Escherichia coli. , 1998 .

[40]  R. Rappuoli,et al.  c‐Src/Lyn kinases activate Helicobacter pylori CagA through tyrosine phosphorylation of the EPIYA motifs , 2002, Molecular microbiology.

[41]  J. Nowak,et al.  Estimates of Helicobacter pylori densities in the gastric mucus layer by PCR, histologic examination, and CLOtest. , 1997, American journal of clinical pathology.

[42]  S. Falkow,et al.  Helicobacter pylori attachment to gastric cells induces cytoskeletal rearrangements and tyrosine phosphorylation of host cell proteins. , 1996, Proceedings of the National Academy of Sciences of the United States of America.

[43]  S. Falkow,et al.  Altered states: involvement of phosphorylated CagA in the induction of host cellular growth changes by Helicobacter pylori. , 1999, Proceedings of the National Academy of Sciences of the United States of America.

[44]  M. Blaser,et al.  Epithelial attachment alters the outcome of Helicobacter pylori infection. , 1998, Proceedings of the National Academy of Sciences of the United States of America.

[45]  A. Lee,et al.  Campylobacter pyloridis and gastritis: association with intercellular spaces and adaptation to an environment of mucus as important factors in colonization of the gastric epithelium. , 1986, The Journal of infectious diseases.

[46]  G. Tytgat,et al.  Electron microscopic study of association between Helicobacter pylori and gastric and duodenal mucosa. , 1994, Journal of clinical pathology.

[47]  R. Hunt,et al.  The role of Helicobacter pylori in pathogenesis: the spectrum of clinical outcomes. , 1996, Scandinavian journal of gastroenterology. Supplement.

[48]  C. Abnet,et al.  Interleukin-1B Polymorphisms and Gastric Cancer Risk—A Meta-analysis , 2006, Cancer Epidemiology Biomarkers & Prevention.

[49]  K. Turksen,et al.  Isolation and characterization , 2006 .

[50]  H. Aburatani,et al.  Helicobacter pylori CagA interacts with E-cadherin and deregulates the β-catenin signal that promotes intestinal transdifferentiation in gastric epithelial cells , 2007, Oncogene.

[51]  R. Haas,et al.  Translocation of Helicobacter pylori CagA into gastric epithelial cells by type IV secretion. , 2000, Science.

[52]  John Bertin,et al.  Nod1 responds to peptidoglycan delivered by the Helicobacter pylori cag pathogenicity island , 2004, Nature Immunology.

[53]  D. Beier,et al.  Acid-responsive gene regulation in the human pathogen Helicobacter pylori. , 2006, Journal of biotechnology.

[54]  J. Sung,et al.  Isolation of Helicobacter pylori from vomitus in children and its implication in gastro-oral transmission , 1999, American Journal of Gastroenterology.

[55]  T. H. Nguyen,et al.  Recovery from gastric mucus depletion in the intact guinea pig mucosa , 2003, Scandinavian journal of gastroenterology.

[56]  R. Rappuoli,et al.  The Neutrophil-Activating Protein (Hp-Nap) of Helicobacter pylori Is a Protective Antigen and a Major Virulence Factor , 2000, The Journal of experimental medicine.

[57]  M. Carrington,et al.  Interleukin-1 polymorphisms associated with increased risk of gastric cancer , 2000, Nature.

[58]  D. Jonkers,et al.  Double gastric infection with Helicobacter pylori and non‐Helicobacter pylori bacteria during acid‐suppressive therapy: increase of pro‐inflammatory cytokines and development of atrophic gastritis , 2001, Alimentary pharmacology & therapeutics.

[59]  M. Hatakeyama Helicobacter pylori CagA--a potential bacterial oncoprotein that functionally mimics the mammalian Gab family of adaptor proteins. , 2003, Microbes and infection.

[60]  E. El-Omar,et al.  Helicobacter pylori infection and abnormalities of acid secretion in patients with duodenal ulcer disease. , 1995, Gastroenterology.

[61]  Takeshi Azuma,et al.  SHP-2 Tyrosine Phosphatase as an Intracellular Target of Helicobacter pylori CagA Protein , 2001, Science.

[62]  R. Hunt,et al.  Meta-analysis of the relationship between cagA seropositivity and gastric cancer. , 2003, Gastroenterology.

[63]  L. Hansson,et al.  Gastric cancer and human leukocyte antigen: distinct DQ and DR alleles are associated with development of gastric cancer and infection by Helicobacter pylori. , 2001, Cancer research.

[64]  M. Reilly,et al.  Helicobacter pylori status in family members as risk factors for infection in children , 2005, Epidemiology and Infection.

[65]  J. Goedert,et al.  Increased risk of noncardia gastric cancer associated with proinflammatory cytokine gene polymorphisms. , 2003, Gastroenterology.

[66]  M. Stephens,et al.  Traces of Human Migrations in Helicobacter pylori Populations , 2003, Science.

[67]  T. Hirayama,et al.  Helicobacter pylori Vacuolating Cytotoxin Induces Activation of the Proapoptotic Proteins Bax and Bak, Leading to Cytochrome c Release and Cell Death, Independent of Vacuolation* , 2006, Journal of Biological Chemistry.

[68]  T. Ohkusa,et al.  Helicobacter pylori infection induces duodenitis and superficial duodenal ulcer in Mongolian gerbils. , 2003, Gut.

[69]  P. Lupetti,et al.  Helicobacter pylori toxin VacA is transferred to host cells via a novel contact‐dependent mechanism , 2004, Cellular microbiology.

[70]  E. El-Omar,et al.  A functional polymorphism of toll-like receptor 4 gene increases risk of gastric carcinoma and its precursors. , 2007, Gastroenterology.

[71]  M. Syvanen,et al.  Modification of Helicobacter pylori outer membrane protein expression during experimental infection of rhesus macaques , 2004, Proceedings of the National Academy of Sciences of the United States of America.

[72]  M. Blaser The versatility of Helicobacter pylori in the adaptation to the human stomach. , 1997, Journal of physiology and pharmacology : an official journal of the Polish Physiological Society.

[73]  A. Zuckerman,et al.  IARC Monographs on the Evaluation of Carcinogenic Risks to Humans , 1995, IARC monographs on the evaluation of carcinogenic risks to humans.

[74]  Takeshi Azuma,et al.  Biological activity of the Helicobacter pylori virulence factor CagA is determined by variation in the tyrosine phosphorylation sites , 2002, Proceedings of the National Academy of Sciences of the United States of America.

[75]  L. Dai,et al.  Association of interleukin‐1 gene polymorphisms with gastric cancer: A meta‐analysis , 2007, International journal of cancer.

[76]  E. El-Omar,et al.  Role of the polymorphic IL‐1B, IL‐1RN and TNF‐A genes in distal gastric cancer in Mexico , 2005, International journal of cancer.

[77]  C. Vindigni,et al.  cagA positive and negative Helicobacter pyloristrains are simultaneously present in the stomach of most patients with non-ulcer dyspepsia: relevance to histological damage , 1998, Gut.

[78]  Karen M. Ottemann,et al.  Helicobacter pylori Uses Motility for Initial Colonization and To Attain Robust Infection , 2002, Infection and Immunity.

[79]  Phenotypic Variation in Molecular Mimicry betweenHelicobacter pylori Lipopolysaccharides and Human Gastric Epithelial Cell Surface Glycoforms , 2002, The Journal of Biological Chemistry.

[80]  E. El-Omar The importance of interleukin 1β inHelicobacter pylori associated disease , 2001, Gut.

[81]  Daniel Falush,et al.  An African origin for the intimate association between humans and Helicobacter pylori , 2007, Nature.

[82]  M. Naumann,et al.  Translocation of the Helicobacter pylori CagA protein in gastric epithelial cells by a type IV secretion apparatus , 2000, Cellular microbiology.

[83]  Y. Shiratori,et al.  Virulence Factors of Helicobacter pylori Responsible for Gastric Diseases in Mongolian Gerbil , 2000, The Journal of experimental medicine.

[84]  L. Brown Helicobacter pylori: epidemiology and routes of transmission. , 2000, Epidemiologic reviews.

[85]  M. Blaser,et al.  Mosaicism in Vacuolating Cytotoxin Alleles of Helicobacter pylori , 1995, The Journal of Biological Chemistry.

[86]  C. Sasakawa,et al.  Role of Peyer's patches in the induction of Helicobacter pylori-induced gastritis , 2007, Proceedings of the National Academy of Sciences.

[87]  C. Prinz,et al.  Helicobacter pylori HopH (OipA) and bacterial pathogenicity: genetic and functional genomic analysis of hopH gene polymorphisms. , 2006, The Journal of infectious diseases.

[88]  P. Bardhan Epidemiological features of Helicobacter pylori infection in developing countries. , 1997, Clinical infectious diseases : an official publication of the Infectious Diseases Society of America.

[89]  R. Rappuoli,et al.  Tyrosine phosphorylation of the Helicobacter pylori CagA antigen after cag-driven host cell translocation. , 2000, Proceedings of the National Academy of Sciences of the United States of America.

[90]  R. Peek,et al.  Helicobacter pylori flagellin evades toll-like receptor 5-mediated innate immunity. , 2004, The Journal of infectious diseases.

[91]  M. Blaser,et al.  Infection with Helicobacter pylori strains possessing cagA is associated with an increased risk of developing adenocarcinoma of the stomach. , 1995, Cancer research.

[92]  J. Bergelson,et al.  Virus-Induced Abl and Fyn Kinase Signals Permit Coxsackievirus Entry through Epithelial Tight Junctions , 2006, Cell.

[93]  C. Josenhans,et al.  The spatial orientation of Helicobacter pylori in the gastric mucus. , 2004, Proceedings of the National Academy of Sciences of the United States of America.

[94]  J. Sung,et al.  Association of interleukin 1B gene polymorphism and gastric cancers in high and low prevalence regions in China. , 2003, Gut.

[95]  G. Rocha,et al.  IL1B and IL1RN polymorphic genes and Helicobacter pylori cagA strains decrease the risk of reflux esophagitis. , 2004, Gastroenterology.

[96]  E. Cascales,et al.  Biogenesis, architecture, and function of bacterial type IV secretion systems. , 2005, Annual review of microbiology.

[97]  T. Borén,et al.  Helicobacter pylori is invasive and it may be a facultative intracellular organism , 2007, Cellular microbiology.

[98]  M. Borodovsky,et al.  cag, a pathogenicity island of Helicobacter pylori, encodes type I-specific and disease-associated virulence factors. , 1996, Proceedings of the National Academy of Sciences of the United States of America.

[99]  K. Ottemann,et al.  Colonization and Inflammation Deficiencies in Mongolian Gerbils Infected by Helicobacter pylori Chemotaxis Mutants , 2005, Infection and Immunity.

[100]  R. Rappuoli,et al.  Selective Inhibition of Ii-dependent Antigen Presentation by Helicobacter pylori Toxin VacA , 1998, The Journal of experimental medicine.

[101]  C. Josenhans,et al.  Rapid Loss of Motility of Helicobacter pylori in the Gastric Lumen In Vivo , 2005, Infection and Immunity.

[102]  G. Rieder,et al.  Genetic or chemical hypochlorhydria is associated with inflammation that modulates parietal and G-cell populations in mice. , 2002, Gastroenterology.

[103]  D. Czajkowsky,et al.  The vacuolating toxin from Helicobacter pylori forms hexameric pores in lipid bilayers at low pH. , 1999, Proceedings of the National Academy of Sciences of the United States of America.

[104]  M. Blaser,et al.  Relation between Helicobacter pylori cagA status and risk of peptic ulcer disease. , 2002, American journal of epidemiology.

[105]  D. Morgan,et al.  Cytotoxic activity in broth-culture filtrates of Campylobacter pylori. , 1988, Journal of medical microbiology.

[106]  S. Guadagnini,et al.  Role of AmiA in the Morphological Transition of Helicobacter pylori and in Immune Escape , 2006, PLoS pathogens.

[107]  Y. Yamaji,et al.  CagA protein secreted by the intact type IV secretion system leads to gastric epithelial inflammation in the Mongolian gerbil model , 2006, The Journal of pathology.

[108]  L. Hammarström,et al.  Helicobacter pylori SabA Adhesin in Persistent Infection and Chronic Inflammation , 2002, Nature Reviews Molecular Cell Biology.

[109]  S. Falkow,et al.  Vacuolating Cytotoxin of Helicobacter pylori Plays a Role during Colonization in a Mouse Model of Infection , 2001, Infection and Immunity.

[110]  I. Helander,et al.  Low biological activity of Helicobacter pylori lipopolysaccharide , 1992, Infection and immunity.

[111]  A. Lee,et al.  The development of atrophic gastritis—Helicobacter pylori and the effects of acid suppressive therapy , 1995, Alimentary pharmacology & therapeutics.

[112]  E. El-Omar,et al.  Interleukin 1Β proinflammatory genotypes protect against gastro-oesophageal reflux disease through induction of corpus atrophy , 2005, Gut.

[113]  M. Camorlinga-Ponce,et al.  Topographical localisation of cagA positive and cagA negative Helicobacter pylori strains in the gastric mucosa; an in situ hybridisation study , 2004, Journal of Clinical Pathology.

[114]  J. Parsonnet,et al.  Acquisition of Helicobacter pylori Infection in Rhesus Macaques Is Most Consistent with Oral-Oral Transmission , 2006, Journal of Clinical Microbiology.

[115]  R. Seruca,et al.  Helicobacter pylori Induces Gastric Epithelial Cell Invasion in a c-Met and Type IV Secretion System-dependent Manner* , 2006, Journal of Biological Chemistry.

[116]  L. Hou,et al.  Mannose‐binding lectin‐2 genetic variation and stomach cancer risk , 2006, International journal of cancer.

[117]  T. Cover,et al.  Acid-induced Dissociation of VacA, the Helicobacter pylori Vacuolating Cytotoxin, Reveals Its Pattern of Assembly , 1997, The Journal of cell biology.

[118]  S. Falkow,et al.  pH-Regulated Gene Expression of the Gastric Pathogen Helicobacter pylori , 2003, Infection and Immunity.

[119]  M. Blaser,et al.  Heightened inflammatory response and cytokine expression in vivo to cagA+ Helicobacter pylori strains. , 1995, Laboratory investigation; a journal of technical methods and pathology.

[120]  W. Birchmeier,et al.  Helicobacter pylori CagA protein targets the c-Met receptor and enhances the motogenic response , 2003, The Journal of cell biology.

[121]  D. Graham,et al.  Challenge model for Helicobacter pylori infection in human volunteers , 2004, Gut.

[122]  J. Crabtree,et al.  Immunology of Helicobacter pylori: insights into the failure of the immune response and perspectives on vaccine studies. , 2007, Gastroenterology.

[123]  H. Mollenkopf,et al.  Cholesterol glucosylation promotes immune evasion by Helicobacter pylori , 2006, Nature Medicine.

[124]  M. Kidd,et al.  Determinants and consequences of different levels of CagA phosphorylation for clinical isolates of Helicobacter pylori. , 2004, Gastroenterology.

[125]  T. Haggerty,et al.  Fecal and oral shedding of Helicobacter pylori from healthy infected adults. , 1999, JAMA.

[126]  H. Aburatani,et al.  Functional antagonism between Helicobacter pylori CagA and vacuolating toxin VacA in control of the NFAT signaling pathway in gastric epithelial cells. , 2005, Proceedings of the National Academy of Sciences of the United States of America.

[127]  J. Pinkner,et al.  Type 1 pilus‐mediated bacterial invasion of bladder epithelial cells , 2000, The EMBO journal.

[128]  C. Caldas,et al.  Helicobacter pylori and interleukin 1 genotyping: an opportunity to identify high-risk individuals for gastric carcinoma. , 2002, Journal of the National Cancer Institute.

[129]  E. Kuipers,et al.  Role of the Helicobacter pylori outer-membrane proteins AlpA and AlpB in colonization of the guinea pig stomach. , 2004, Journal of medical microbiology.

[130]  T. Azuma,et al.  The role of the HLA‐DQA1 gene in resistance to atrophic gastritis and gastric adenocarcinoma induced by Helicobacter pylori infection , 1998, Cancer.

[131]  H. Steer Surface morphology of the gastroduodenal mucosa in duodenal ulceration. , 1984, Gut.

[132]  S. Brandt,et al.  Activation of Abl by Helicobacter pylori: a novel kinase for CagA and crucial mediator of host cell scattering. , 2007, Gastroenterology.

[133]  E. Kuipers,et al.  The Functional Status of the Helicobacter pylori sabB Adhesin Gene as a Putative Marker for Disease Outcome , 2004, Helicobacter.

[134]  R. Rappuoli,et al.  A structural overview of the Helicobacter cytotoxin. , 2000, International journal of medical microbiology : IJMM.

[135]  D. Forman,et al.  Role of Helicobacter pylori CagA+ strains and risk of adenocarcinoma of the stomach and esophagus , 2003 .

[136]  E. Kuipers,et al.  Atrophic gastritis and Helicobacter pylori infection in patients with reflux esophagitis treated with omeprazole or fundoplication. , 1996, The New England journal of medicine.

[137]  Y. Hirooka,et al.  Interleukin-8 Promoter Polymorphism Increases the Risk of Atrophic Gastritis and Gastric Cancer in Japan , 2005, Cancer Epidemiology Biomarkers & Prevention.

[138]  Ruslan Medzhitov,et al.  Toll-like receptors: linking innate and adaptive immunity. , 2005, Advances in experimental medicine and biology.

[139]  E. El-Omar,et al.  Helicobacter pylori infection and chronic gastric acid hyposecretion. , 1997, Gastroenterology.

[140]  E. Fontham,et al.  Interleukin-1β and Interleukin-1 Receptor Antagonist Gene Polymorphisms and Gastric Cancer: A Meta-analysis , 2006, Cancer Epidemiology Biomarkers & Prevention.

[141]  R. Haas,et al.  Helicobacter pylori Vacuolating Cytotoxin Inhibits T Lymphocyte Activation , 2003, Science.

[142]  G. Rieder,et al.  Helicobacter pylori cag-type IV secretion system facilitates corpus colonization to induce precancerous conditions in Mongolian gerbils. , 2005, Gastroenterology.

[143]  C. Sasakawa,et al.  Grb2 is a key mediator of helicobacter pylori CagA protein activities. , 2002, Molecular cell.

[144]  H. Mobley,et al.  Helicobacter pylori urease: properties and role in pathogenesis. , 1991, Scandinavian journal of gastroenterology. Supplement.

[145]  C. Sasakawa,et al.  Interaction of CagA with Crk plays an important role in Helicobacter pylori–induced loss of gastric epithelial cell adhesion , 2005, The Journal of experimental medicine.

[146]  D. Forman,et al.  Role of Helicobacter pylori CagA+ strains and risk of adenocarcinoma of the stomach and esophagus. , 2001, International journal of cancer.

[147]  D. Schwartz,et al.  Toll-like receptor 4 polymorphisms and atherogenesis. , 2002, The New England journal of medicine.

[148]  T. Hirayama,et al.  Mice deficient in protein tyrosine phosphatase receptor type Z are resistant to gastric ulcer induction by VacA of Helicobacter pylori , 2003, Nature Genetics.

[149]  C. Caldas,et al.  A proinflammatory genetic profile increases the risk for chronic atrophic gastritis and gastric carcinoma. , 2003, Gastroenterology.

[150]  A. Axon,et al.  Why does Japan have a high incidence of gastric cancer? Comparison of gastritis between UK and Japanese patients , 2006, Gut.

[151]  Elisabeth M Bik,et al.  Molecular analysis of the bacterial microbiota in the human stomach. , 2006, Proceedings of the National Academy of Sciences of the United States of America.

[152]  Atosa Ahmadi,et al.  Helicobacter pylori Accumulates Photoactive Porphyrins and Is Killed by Visible Light , 2005, Antimicrobial Agents and Chemotherapy.

[153]  D. Schwartz,et al.  Relevance of mutations in the TLR4 receptor in patients with gram-negative septic shock. , 2002, Archives of internal medicine.

[154]  H. Brenner,et al.  Is Helicobacter pylori infection a necessary condition for noncardia gastric cancer? , 2004, American journal of epidemiology.

[155]  S. Falkow,et al.  Induction of host signal transduction pathways by Helicobacter pylori. , 1997, Proceedings of the National Academy of Sciences of the United States of America.

[156]  W. Birchmeier,et al.  Coupling of Gab1 to C-Met, Grb2, and Shp2 Mediates Biological Responses , 2000, The Journal of cell biology.

[157]  L. Engstrand,et al.  SabA Is the H. pylori Hemagglutinin and Is Polymorphic in Binding to Sialylated Glycans , 2006, PLoS pathogens.

[158]  R. Peek,et al.  Differential activation of mitogen-activated protein kinases in AGS gastric epithelial cells by cag+ and cag- Helicobacter pylori. , 1999, Journal of immunology.

[159]  D. Mckay,et al.  Helicobacter spp. from captive bottlenose dolphins (Tursiops spp.) and polar bears (Ursus maritimus). , 2005, Veterinary journal.

[160]  M. Washington,et al.  Activation of β-catenin by carcinogenic Helicobacter pylori , 2005 .

[161]  Yi-ping Lin,et al.  The −251T Allele of the Interleukin-8 Promoter Is Associated with Increased Risk of Gastric Carcinoma Featuring Diffuse-Type Histopathology in Chinese Population , 2005, Clinical Cancer Research.

[162]  R. Melano,et al.  The Helicobacter pylori Chemotaxis Receptor TlpB (HP0103) Is Required for pH Taxis and for Colonization of the Gastric Mucosa , 2006, Journal of bacteriology.

[163]  C. Sasakawa,et al.  Helicobacter pylori Caga Protein Can Be Tyrosine Phosphorylated in Gastric Epithelial Cells , 2000, The Journal of experimental medicine.

[164]  C. Herzog,et al.  [Interleukin 1 and tumor necrosis factor]. , 1987, Zeitschrift fur Rheumatologie.

[165]  G. Matullo,et al.  Interleukin-1 Gene Polymorphisms and Gastric Cancer Risk in a High-Risk Italian Population , 2005, The American Journal of Gastroenterology.

[166]  M. Blaser,et al.  Helicobacter pylori CagA transfection of gastric epithelial cells induces interleukin‐8 , 2006, Cellular microbiology.

[167]  F. Dewhirst,et al.  Isolation and Characterization of a Helicobacter sp. from the Gastric Mucosa of Dolphins, Lagenorhynchus acutusand Delphinus delphis , 2000, Applied and Environmental Microbiology.

[168]  B. Knapp,et al.  Conservation, localization and expression of HopZ, a protein involved in adhesion of Helicobacter pylori. , 1999, Nucleic acids research.

[169]  Takeshi Azuma,et al.  Helicobacter pylori infection triggers aberrant expression of activation-induced cytidine deaminase in gastric epithelium , 2007, Nature Medicine.

[170]  M. Blaser,et al.  Functional Adaptation of BabA, the H. pylori ABO Blood Group Antigen Binding Adhesin , 2004, Science.

[171]  L. Murray,et al.  Helicobacter pylori infection in children: relation with current household living conditions. , 1996, Gut.

[172]  S. Brandt,et al.  NF-kappaB activation and potentiation of proinflammatory responses by the Helicobacter pylori CagA protein. , 2005, Proceedings of the National Academy of Sciences of the United States of America.