Molecular Mechanisms of Inflammation: Induction, Resolution and Escape by Helicobacter pylori (Current Topics in Microbiology and Immunology, 421)

This book focuses on immune reactions and interactions of humans with __Helicobacter pylori__ - a human pathogen connected to gastritis, peptic ulcers and even gastric cancer. With nearly half of the world’s population colonized, it has been characterized as one of the most successful pathogens for more than 100,000 years of co-evolution with its host. The respective chapters discuss not only how __H. pylori__ infection is considered a paradigm for persistent bacterial infection and chronic inflammation, but also how the infection might be connected to host protection against gastro-esophageal diseases, asthma, and other allergic disease manifestations. Readers will gain essential insights into the roles of specific factors in the immune response and learn about the impact of genetic polymorphisms on the risk of gastric carcinogenesis. In addition, the book discusses the strategies used by this bacterium, which allow it to colonize specific sites in the stomach, interact with the microbiome, evade immune surveillance and undermine the resolution of inflammation during persistent infection. This volume presents a concise summary of recent advances in the areas of induction, resolution and escape of inflammation, innate and adaptive immunity, gastric disease development, as well as treatment and vaccination against __H. pylori__. Accordingly, it offers a valuable asset for scientists and clinicians alike. Foreword: New Directions for Investigating Detrimental and Enabling Interactions Between Helicobacter pylori and Its Host 6 Contents 10 Abbreviations 12 Inflammation, Immunity, and Vaccine Development for the Gastric Pathogen Helicobacter pylori 26 1 Introduction 27 2 Host Immune Response to H. pylori Infection 27 3 Obstacles in Developing H. pylori Vaccine 30 4 Establishing the Principles for H. pylori Vaccination 31 5 Varied Vaccination Strategies Employed in Clinical Trials 32 6 Unique Aspects of a Successful Clinical Trial 35 7 Concluding Remarks 38 References 39 Impact of Helicobacter pylori Virulence Factors on the Host Immune Response and Gastric Pathology 45 1 Introduction 46 2 Vacuolating Cytotoxin 47 2.1 Heterogeneity and the Epidemiology of Gastric Disease 47 2.2 Animal Models and Cell Biology 48 3 Cag Pathogenicity Island 49 3.1 Epidemiology 49 3.2 Genetic Organization 50 3.3 T4SS 50 3.4 T4SS Effectors 54 3.5 Hijacking Host Signaling 56 4 Outer Membrane Proteins (OMPs) 57 4.1 Paralogous OMP Gene Families 57 4.2 H. pylori OMPs and Clinical Disease 57 4.3 OMPs and Pathogenesis 58 5 Modulation of the Host Response: Bacterial Virulence from the Bacterial Perspective 62 6 Concluding Remarks 65 References 66 Genetic Polymorphisms in Inflammatory and Other Regulators in Gastric Cancer: Risks and Clinical Consequences 77 1 Introduction 78 2 Gastric Cancer Development is Related to H. pylori Infection 79 3 H. pylori Virulence Factors and Gastric Cancer Risk 79 4 Host Genetic Susceptibility to Gastric Cancer 82 4.1 Immuno-Regulatory Cytokines 82 4.2 Pattern Recognition Receptors (PRRs) 86 4.3 DNA Repair Enzymes 87 4.4 Genetic Polymorphisms in Other Factors 89 5 Concluding Remarks 89 References 90 MALT Lymphoma as a Model of Chronic Inflammation-Induced Gastric Tumor Development 101 1 Introduction 102 2 Clinical and Pathological Features 103 3 Pathogenesis 105 3.1 First Step: Gastric Acquisition of MALT 105 3.2 Second Step: Acquisition of Genetic Abnormalities 108 3.3 Third Step: Dysregulation of NF-κB Signaling 113 4 Treatment and Follow-up 119 5 Concluding Remarks 120 References 121 Crosstalk Between DNA Damage and Inflammation in the Multiple Steps of Gastric Carcinogenesis 131 1 Introduction 132 2 H. pylori and Inflammation 132 3 Mechanisms of DNA Damage 135 3.1 Oxidative Stress 136 3.2 DNA-Modifying Enzymes 139 3.3 DNA Repair System 140 4 Genetic Alterations During Gastric Carcinogenesis 143 4.1 Mutational Landscape of Gastric Cancer 143 4.2 Stem Cells 146 5 Concluding Remarks 148 References 149 Importance of Toll-like Receptors in Pro-inflammatory and Anti-inflammatory Responses by Helicobacter pylori Infection 162 1 Introduction 163 2 Overview of TLRs 164 3 Lipopolysaccharide and TLR Interaction 165 4 TLRs and H. pylori Research 167 5 Microbes Drive TLR Evolution 168 6 TLR2/TLR10 and H. pylori LPS 170 7 TLR10 and Anti-inflammatory Responses 172 8 Concluding Remarks 176 References 176 Role of NOD1 and ALPK1/TIFA Signalling in Innate Immunity Against Helicobacter pylori Infection 182 1 Introduction 183 2 H. pylori Induction of NF-κB Signalling in Human Epithelial Cells 185 2.1 The H. pylori cagPAI Is Required for Induction of NF-κB Activation in Epithelial Cells 185 2.2 cagPAI-Encoded Proteins Associated with NF-κB Activation 186 2.3 H. pylori Activates the NF-κB Pathway in Epithelial Cells via NOD1 187 3 Role of NOD1 in Host Immune Responses to H. pylori In Vivo 189 4 TIFA, A New Host Factor Mediating NF-κB-Dependent Responses to H. pylori Infection 191 5 Concluding Remarks 193 References 194 Carbohydrate-Dependent and Antimicrobial Peptide Defence Mechanisms Against Helicobacter pylori Infections 201 1 Introduction 202 2 Mucus, Mucins and Glycolipids 203 3 Helicobacter pylori Components Involved in Adhesion 204 3.1 The Blood Group-Binding Adhesin BabA 206 3.2 The Sialic Acid-Binding Adhesin SabA 207 3.3 Other H. pylori Molecules Involved in Adhesion to Host Structures 208 3.4 Lipopolysaccharide (LPS) 208 3.5 Secreted H. pylori Proteins that Bind to Glycans 209 4 Regulation and Consequences of H. pylori Binding to Mucins 209 4.1 Infection Induced Changes in Mucin Production, Localization and Glycosylation 210 4.2 Competition Between Binding to Mucins and Glycolipids 210 4.3 Regulation of H. pylori Adhesin Expression 211 4.4 Effects of Glycans on H. pylori Growth 213 5 Antimicrobial Peptides in the Gastric Mucosa 213 6 Bactericidal Activity of AMPs Against H. pylori 216 7 H. pylori-Mediated Regulation of Defensin Expression 217 8 AMP Regulation of Immune Cell Functions 218 9 AMPs and Glycans as Therapeutics for Eradication of H. pylori 218 10 Concluding Remarks 219 References 219 The Sweeping Role of Cholesterol Depletion in the Persistence of Helicobacter pylori Infections 230 1 Introduction 231 2 Inflammation Induced by H. pylori 231 3 Epithelial Defense Molecules: Antimicrobial Potential Against H. pylori 234 4 Cholesterol Glucosides in H. pylori: Implications for Virulence 235 5 H. pylori Targets Host Cholesterol to Block the Epithelial Response to IFN-γ and Related Cytokines 238 6 Concluding Remarks 241 References 242 Helicobacter pylori Deregulates T and B Cell Signaling to Trigger Immune Evasion 249 1 Introduction 250 2 B and T Lymphocyte Development 251 2.1 B Lymphocyte 251 2.2 T Lymphocyte 253 3 B and T Lymphocyte Activation 254 3.1 B Lymphocyte 255 3.2 T Lymphocyte 255 4 T Cell Subsets and Reprogramming 260 4.1 T Cell Subsets 260 5 Reprogramming and Plasticity 264 6 H. pylori Induction and Evasion of the Host Immune Response 265 7 Concluding Remarks 272 References 273 Mechanisms of Inflammasome Signaling, microRNA Induction and Resolution of Inflammation by Helicobacter pylori 286 1 Introduction 287 2 Inflammasome Activation Through NOD2 and TLR2 Signal Transduction 289 3 Role of microRNAs in H. pylori Interaction with Host Cells 292 4 H. pylori Manipulates TLR Signaling and Bacterial Recognition 298 5 Pro- and Anti-inflammatory Cytokine Signaling by H. pylori 300 6 Resolution of Inflammation by H. pylori 305 7 Concluding Remarks 308 References 308 Impact of the Gastrointestinal Microbiome in Health and Disease: Co-evolution with the Host Immune System 322 1 Introduction 323 2 Early Life Colonization and H. pylori Infection in Childhood 323 3 H. pylori and Immunoregulation 324 4 Helicobacter pylori and the Oesophageal Microbiome 327 5 Helicobacter pylori and the Gastric Microbiome 329 5.1 The Gastric Cancer Microbiome 331 6 Helicobacter pylori and the Colonic Microbiome 331 7 Concluding Remarks 332 References 333 Resolution of Gastric Cancer-Promoting Inflammation: A Novel Strategy for Anti-cancer Therapy 338 1 Introduction 339 2 Inflammatory Mediators of Gastritis and the Tumor Microenvironment (TME) 340 2.1 Chronic Inflammation in H. pylori 340 2.2 The TME in Gastric Cancer 343 3 Anti-cancer Strategies Targeting the Pro-inflammatory Mediators in the TME 346 3.1 Cell Signaling Inhibitors 346 3.2 Cytokine Antagonists (IL-1, IL-6, IL-18, TNF) 346 3.3 Non-steroidal Anti-inflammatory Drugs 349 4 Strategies Targeting Growth Factors Involved in Angiogenesis 353 4.1 Growth Factors as Target (VEGF/VEGFR2, CSF1/CSF1R, EGF/EGFR) 353 4.2 Strategies Inhibiting M1 to M2 Transitions and Promoting M1 Phenotype 356 4.3 Inhibition of Myeloid-derived Suppressor Cells (MDSCs) 357 4.4 Targeting Chemokines and Their Receptors 357 5 Enhancing Anti-tumor Immunity (Therapy-Induced Inflammation) 360 5.1 Checkpoint Inhibitors (Anti-PD-1/L1, Anti-CTLA4) 360 5.2 Other Immunotherapies—Immunoconjugates 361 6 Concluding Remarks 362 References 363 Front Matter ....Pages i-xxiv Inflammation, Immunity, and Vaccine Development for the Gastric Pathogen Helicobacter pylori (Tamaki Ikuse, Thomas G. Blanchard, Steven J. Czinn)....Pages 1-19 Impact of Helicobacter pylori Virulence Factors on the Host Immune Response and Gastric Pathology (Sundus Javed, Emma C. Skoog, Jay V. Solnick)....Pages 21-52 Genetic Polymorphisms in Inflammatory and Other Regulators in Gastric Cancer: Risks and Clinical Consequences (Karolina Rudnicka, Steffen Backert, Magdalena Chmiela)....Pages 53-76 MALT Lymphoma as a Model of Chronic Inflammation-Induced Gastric Tumor Development (Lukas Marcelis, Thomas Tousseyn, Xavier Sagaert)....Pages 77-106 Crosstalk Between DNA Damage and Inflammation in the Multiple Steps of Gastric Carcinogenesis (Olga Sokolova, Michael Naumann)....Pages 107-137 Importance of Toll-like Receptors in Pro-inflammatory and Anti-inflammatory Responses by Helicobacter pylori Infection (Hiroyuki Nagashima, Yoshio Yamaoka)....Pages 139-158 Role of NOD1 and ALPK1/TIFA Signalling in Innate Immunity Against Helicobacter pylori Infection (Le Ying, Richard L. Ferrero)....Pages 159-177 Carbohydrate-Dependent and Antimicrobial Peptide Defence Mechanisms Against Helicobacter pylori Infections (Médea Padra, John Benktander, Karen Robinson, Sara K. Lindén)....Pages 179-207 The Sweeping Role of Cholesterol Depletion in the Persistence of Helicobacter pylori Infections (Pau Morey, Thomas F. Meyer)....Pages 209-227 Helicobacter pylori Deregulates T and B Cell Signaling to Trigger Immune Evasion (Victor E. Reyes, Alex G. Peniche)....Pages 229-265 Mechanisms of Inflammasome Signaling, microRNA Induction and Resolution of Inflammation by Helicobacter pylori (Suneesh Kumar Pachathundikandi, Nicole Blaser, Steffen Backert)....Pages 267-302 Impact of the Gastrointestinal Microbiome in Health and Disease: Co-evolution with the Host Immune System (Georgina L. Hold, Richard Hansen)....Pages 303-318 Resolution of Gastric Cancer-Promoting Inflammation: A Novel Strategy for Anti-cancer Therapy (M. Blanca Piazuelo, Rachel P. Riechelmann, Keith T. Wilson, Holly M. Scott Algood)....Pages 319-359