Allergy Prevention and Exacerbation : The Paradox of Microbial Impact on the Immune System

Allergy is developing into one of the most prevalent diseases affecting individuals in the very early days of life. While the cause of this epidemic is still unclear, it appears that the westernized life style is playing an important role, which includes nutrition, possibly air pollution as well as hygienic conditions. While epidemiologic studies were able to narrow down these factors, basic research discovered novel mechanisms that control the organism ́s tolerance against allergens. Particularly interesting is the role of microorganisms that colonize or infect a host and thereby cause damage and immunological activation followed by sensitization or exacerbation of already existing sensitizations. However at the same time microbial activation of the immune system can help to generate a protective immunity that prevents allergen sensitization. The current book is collecting these evidences and connects epidemiologic and clinical mechanistic knowledge. Only the synthesis of this knowledge will help to find solutions to the ongoing allergy epidemic in terms of public health activities, prevention and therapy. Contents 6 Overview: The Paradox of Microbial Impact on the Immune System in Allergy Prevention and Exacerbation 8 1 Introduction: Allergy Exacerbation Triggers Are Also the Prevention Factors 9 2 Cellular Player: From Genetics to the Immune System 11 3 Protection Against Allergy 12 4 Chronification and Exacerbation of Allergies 13 5 Concluding Remarks and Therapeutic Relevance 14 References 14 Microbial Triggers in Autoimmunity, Severe Allergy, and Autoallergy 17 1 Immune Dysfunction as Underlying Cause of Allergy, Autoimmunity and Autoallergy 18 2 Autoimmunity and Microbial Triggers 20 2.1 Basic Pathogenesis of Autoimmunity 20 2.2 Microbial Triggers in Autoimmunity 21 2.2.1 Bacterial Triggers of Autoimmunity 21 2.2.2 Viral Triggers of Autoimmunity 22 3 Microbial Triggers in Severe Allergy 22 3.1 Atopic Dermatitis 22 3.1.1 Staphylococci 23 3.1.2 Viral Infections 24 3.1.3 Fungi 24 3.2 Allergic Asthma 25 3.2.1 Bacterial Triggers in Allergic Asthma 25 3.2.2 Viral Triggers in Allergic Asthma 26 4 Microbial Triggers in Autoallergy 26 5 Conclusion 28 References 28 Bacterial Allergens 33 1 Introduction 33 2 Atypical Bacterial Pathogens 39 2.1 Chlamydia trachomatis 39 2.2 Chlamydia pneumoniae 40 2.3 Mycoplasma pneumoniae 41 3 Common Bacterial Inhabitants of the Human Respiratory Tract 42 3.1 Staphylococcus aureus 42 3.2 Staphylococcus epidermidis 44 3.3 Haemophilus influenza 44 3.4 Streptococcus pneumoniae 45 3.5 Streptococcus pyogenes 46 3.6 Moraxella catarrhalis 47 3.7 Pseudomonas aeruginosa 47 4 Bacteria Not Related to the Respiratory Tract 48 4.1 Borrelia burgdorferi 48 4.2 Staphylococcus saprophyticus 48 5 Conclusions 49 References 49 Good and Bad Farming: The Right Microbiome Protects from Allergy 57 1 The Hygiene Hypothesis and the Farming Studies 58 2 Good and Bad Farming 59 3 Generic Markers of Microbial Exposure 61 4 Microbial DNA 62 5 Microbial Diversity and Hot Spots of Microbial Exposure 63 6 The Role of Fungi 64 7 The Special Case of Gram-Negative Bacteria and Endotoxin 65 8 Translation from Environmental Microbiota to Mucosal Microbiomes 66 9 Microbial Virulence or Host Factors? 68 10 The Right Microbiome 69 References 70 The Lost Friend: H. pylori 75 1 Background 75 2 H. pylori 76 2.1 Immune Response Against Helicobacter pylori 78 3 Allergy Prevalence Caused by Environmental Impact? 81 4 Helicobacter pylori and Allergy 83 4.1 Human Studies 83 4.2 Animal Studies 86 5 Concluding Remarks 89 References 91 Parasite Mediated Protection Against Allergy 104 1 Introduction 104 2 Epidemiology of Parasite Mediated Protection Against Allergy 106 3 Parasite Mediated Protection Against Allergy in Rodent Models 108 4 Mechanisms of Parasite Mediated Protection Against Allergy 110 4.1 Modulation of the Innate Immune System 110 4.1.1 Epithelial Cells 111 4.1.2 Macrophages 112 4.1.3 Neutrophils and Eosinophils 112 4.1.4 Mast Cells and Basophils 113 4.1.5 Innate Lymphoid Cells 114 4.1.6 Dendritic Cells 114 4.2 Modulation of the Adaptive Immune System 115 4.2.1 Regulatory T-Cells 116 4.2.2 Regulatory B-Cells 117 5 Concluding Remarks and Outlook 117 References 118 Initiation, Persistence and Exacerbation of Food Allergy 126 1 Introduction 127 2 CD4 T Cell Fate Is Determined by DCs Programmed at Barrier Sites: (Do) All Roads Lead to Rome (?) 128 3 Understanding of Memory 130 3.1 Immune Memory in Food Allergy 131 4 Generation and Nature of Memory CD4 T and B Cells 132 4.1 Heterogeneity of Memory CD4 T Cells 132 4.2 The Elusive IgE+ Memory B Cell 135 5 Activation of Memory Responses in Food Allergy 138 5.1 Therapeutic Implications/Prospects 139 6 Conclusion 141 References 142 The Role of the Gut in Type 2 Immunity 150 1 Introduction 150 2 The Gut: Site of Tolerance or Induction of Allergic Disorders? 152 2.1 The Fundamental Role of Microbes 152 2.2 Regulatory T Cells: Not Only Foxp3 154 3 Microbial Impact on Allergy on an Epidemiological Perspective 158 4 Non-intestinal Barrier Sites at the Origin of Allergic Disorders 159 5 Conclusion 161 References 162 Aryl Hydrocarbon Receptor: An Environmental Sensor in Control of Allergy Outcomes 171 1 AhR: A Pleiotropic Immune Regulator 172 1.1 AhR Structure and Conventional AhR Signaling Pathway 172 1.2 Exogenous and Endogenous AhR Ligands 175 1.3 AhR Plasticity: Alternative AhR Transcriptional Responses 176 2 AhR: A Multitasking Effector in Allergy Regulation 178 2.1 Ubiquitous AhR Expression and Activity in Multiple Cell Types Impacting on Allergic Responses 178 2.2 AhR Role in Allergic Asthma 181 2.3 AhR Role in Atopic Dermatitis 183 2.4 AhR Role in Food Allergy 184 3 Conclusions 185 References 186 The Gut Microbiome and Its Marriage to the Immune System: Can We Change It All? 194 1 Introduction: The Gastrointestinal Microbial Colonization 194 2 Early Microbial Colonization and Immune Programming 195 3 Intestinal Microbiota and Immune System Interactions 197 3.1 Microbial Effects on Innate Immune Cells 198 3.2 Cross-Talk Between the Gut Microbes and Adaptive Immune Cells 199 4 Factors Associated with Changes of the Gut Microbiota 200 5 Clinical Implications: Microbiota Modulation Potentially Influencing Immunological Diseases 202 6 Conclusion and Future Outlook 203 References 204 Specific Therapies for Asthma Endotypes: A New Twist in Drug Development 212 1 Key Mechanisms of Asthma 213 2 Type 2 Biomarkers in Asthma 215 3 Approaches to Target Asthma Subgroups by Biologicals 216 3.1 Th2 Pattern and Related Biomarkers 216 3.2 Approaches to Target Immunoglobulin E 217 3.3 Approaches to Target Th2 Key Cytokines IL-4 and IL-13 222 3.4 Approaches to Target IL-5 224 3.5 Approaches to Target TSLP 226 3.6 Approaches to Target CD25 227 3.7 Approaches to Target OX40L 228 3.8 Approaches to Target GATA-3 228 4 Biologic Approaches in Non-Th2 Asthma 229 4.1 Approaches to Target TNF-α 229 4.2 Approaches to Target Th9 Cells 229 4.3 Targeting Neutrophils and Related Microbial Influence 230 4.4 Targeting RSV and Dysbalanced Microbiome 231 References 232 Index 242 Front Matter ....Pages i-vi Overview: The Paradox of Microbial Impact on the Immune System in Allergy Prevention and Exacerbation (Carsten B. Schmidt-Weber)....Pages 1-9 Microbial Triggers in Autoimmunity, Severe Allergy, and Autoallergy (Fariza M. S. Badloe, Sherief R. Janmohamed, Johannes Ring, Jan Gutermuth)....Pages 11-26 Bacterial Allergens (Gómez-Gascón Lidia, Barbara M. Bröker)....Pages 27-50 Good and Bad Farming: The Right Microbiome Protects from Allergy (Markus Johannes Ege)....Pages 51-68 The Lost Friend: H. pylori (Raphaela P. Semper, Markus Gerhard)....Pages 69-97 Parasite Mediated Protection Against Allergy (Julia Esser-von Bieren)....Pages 99-120 Initiation, Persistence and Exacerbation of Food Allergy (Rodrigo Jiménez-Saiz, Derek K. Chu, Susan Waserman, Manel Jordana)....Pages 121-144 The Role of the Gut in Type 2 Immunity (Caspar Ohnmacht)....Pages 145-165 Aryl Hydrocarbon Receptor: An Environmental Sensor in Control of Allergy Outcomes (Marco Gargaro, Matteo Pirro, Giorgia Manni, Antonella De Luca, Teresa Zelante, Francesca Fallarino)....Pages 167-189 The Gut Microbiome and Its Marriage to the Immune System: Can We Change It All? (Eva Untersmayr)....Pages 191-208 Specific Therapies for Asthma Endotypes: A New Twist in Drug Development (Ulrich M. Zissler)....Pages 209-238 Back Matter ....Pages 239-248 Allergy is developing into one of the most prevalent diseases affecting individuals in the very early days of life. While the cause of this epidemic is still unclear, it appears that the westernized life style is playing an important role, which includes nutrition, possibly air pollution as well as hygienic conditions. While epidemiologic studies were able to narrow down these factors, basic research discovered novel mechanisms that control the organismś tolerance against allergens. Particularly interesting is the role of microorganisms that colonize or infect a host and thereby cause damage and immunological activation followed by sensitization or exacerbation of already existing sensitizations. However at the same time microbial activation of the immune system can help to generate a protective immunity that prevents allergen sensitization. The current book is collecting these evidences and connects epidemiologic and clinical mechanistic knowledge. Only the synthesis of this knowledge will help to find solutions to the ongoing allergy epidemic in terms of public health activities, prevention and therapy Allergy is developing into one of the most prevalent diseases affecting individuals in the very early days of life. While the cause of this epidemic is still unclear, it appears that the westernized life style is playing an important role, which includes nutrition, possibly air pollution as well as hygienic conditions. While epidemiologic studies were able to narrow down these factors, basic research discovered novel mechanisms that control the organism㠴olerance against allergens. Particularly interesting is the role of microorganisms that colonize or infect a host and thereby cause damage and immunological activation followed by sensitization or exacerbation of already existing sensitizations. However at the same time microbial activation of the immune system can help to generate a protective immunity that prevents allergen sensitization. The current book is collecting these evidences and connects epidemiologic and clinical mechanistic knowledge. Only the synthesis of this knowledge will help to find solutions to the ongoing allergy epidemic in terms of public health activities, prevention and therapy