Biological DNA Sensor - 1st Edition - ISBN: 9780124047327, 9780124051683

Biological DNA Sensor

1st Edition

The Impact of Nucleic Acids on Diseases and Vaccinology

Editors: Ken Ishii Choon Kit Tang
eBook ISBN: 9780124051683
Hardcover ISBN: 9780124047327
Imprint: Academic Press
Published Date: 7th November 2013
Page Count: 368
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Biological DNA Sensor defines the meaning of DNA sensing pathways and demonstrates the importance of the innate immune responses induced by double stranded DNA (dsDNA) through its influencing functions in disease pathology and immune activity of adjuvants for vaccines.

Though discussed in specific subsections of existing books, dsDNA and its immunogenic properties has never received the complete treatment given in this book. Biological DNA Sensor approaches the impact of dsDNA's immunogenicity on disease and vaccinology holistically. It paints a complete and concise picture on the topic so you can understand this area of study and make more informed choices for your respective research needs. Chapters are authored by researchers who are renowned for their research focus, ensuring that this book provides the most complete views on the topics.

Key Features

  • Multi-authored by a distinguished panel of world-class experts
  • Ideal source of information for those wanting to learn about DNA sensing
  • Provides in-depth explanations of DNA sensing pathways and the innate immune system, bridging the gap between them


Students, scientists and practitioners in innate immunology, autoimmune diseases and vaccinology

Table of Contents

List of Contributors


Section A: The Discovery of dsDNA Immunogenicity and the Definition of DNA Sensing Pathways

Chapter 1. Route to Discovering the Immunogenic Properties of DNA from TLR9 to Cytosolic DNA Sensors


The Importance of the Innate Immune System

Endosomal-Membrane Bound DNA Sensor – TLR9

Cytosolic DNA Sensors




Chapter 2. The PYHIN Family of Molecules and their Functions Sensing dsDNA


Members of the Pyhin Family

Structural Basis of DNA Recognition by PYHIN Proteins

Microbial DNA Sensing and Signaling by PYHIN Proteins

Transcriptional Regulation by PYHIN Proteins

Role of PYHIN Proteins in the Development of Autoimmunity

Regulation of PYHIN Proteins



Chapter 3. Cytosolic DNA-Sensing and the STING Pathway


The Toll-Like Pathway: TLR9 and CpG DNA

The STING Pathway and Intracellular DNA Signaling

STING and Inflammatory Disease

Other Sensors of Intracellular DNA



Chapter 4. Regulation of Intracellular dsDNA-Induced Innate Immune Responses by Autophagy-Related Proteins

Part I. Autophagy-Related Proteins and STING-Dependent IFN Responses

Part II. Autophagy and STING-Dependent Bactericidal Responses

Part III. Autophagy and AIM2-Dependent Inflammatory Responses



Section B: dsDNA and Its Part in Modulating Human Diseases

Chapter 5. Host DNA Induced Inflammation and Autoimmune Diseases


The Type I IFN System as the Crux of Autoimmunity

Self and Non-Self-DNA Recognition

Heterogeneity in Innate Receptors for DNA

Mechanisms Underlying Host DNA Induced Inflammation and Autoimmunity

Conclusions and Future Perspectives


Chapter 6. Toll-Like Receptor 9 and Toll-Like Receptor 7 in the Development and Regulation of Systemic Autoimmune Disease


Nucleic Acid Sensing TLRs

Immune Complex Activation of pDCs and Type I IFN

Activation of Autoreactive B Cells Depends on BCR/TLR Co-Engagement

Autoantigens and TLR Activation

Aberrant Self-Antigen Clearance and Detection

Paradoxical Roles of TLR9 and TLR7 in Murine Models of SLE

Critical Role for B Cells in TLR-Mediated Regulation of Autoimmune Disease and TLR9-Dependent Suppression of Autoimmune Disease

Cell Intrinsic Regulation of TLR9 and TLR7 in B Cells

Compartmental Restriction of TLR Responses

Summary and Unanswered Questions


Chapter 7. Bacterial Infections and the DNA Sensing Pathway


The Role of TLR9 in Bacterial Infections

The AIM2 Inflammasome as a Sensor of Bacterial DNA

Sting-Dependent Cytosolic DNA Sensors and Type I IFN Responses During Bacterial Infections




Chapter 8. Viral Infections and the DNA Sensing Pathway: Lessons from Herpesviruses and Beyond


Innate Immunological Recognition of Herpesvirus DNA

DNA Sensors Involved in Recognition of Herpesvirus DNA

Role for Sting in the Response to Intracellular DNA Sensing

Roles of Known DNA Sensors in Herpesvirus Infection Independent of their Role as PRRs

Viral Evasion of DNA-Driven Innate Immune Responses

DNA Sensing Beyond Herpesviruses

Concluding Remarks



Chapter 9. Cancer Pathogenesis and DNA Sensing

IFN-Inducing Cytosolic DNA Sensors

Mediators of IFN-Inducing Cytosolic DNA Sensors

STING and TRIF Pathways


ProInflammatory Cytokines

Inflammasome-Inducing Cytosolic DNA Sensors



Chapter 10. DNA Damage Responses in Atherosclerosis


Evidence of DNA Damage in Atherosclerosis

Types of DNA Damage

Mitochondrial DNA Damage

DNA Damage Responses in Atherosclerosis

DNA Damage Sensing and Inflammation in Atherosclerosis




Section C: The DNA Sensing Pathway and Its Impact on Vaccinology

Chapter 11. DNA Vaccine: Does it Target the Double Stranded-DNA Sensing Pathway?


DNA Vaccines: Proof of Concept

DNA Vaccines: Mouse vs. Man

What Immunological Responses are Triggered after DNA Vaccination?

Cytosolic Double Stranded (ds)-DNA Sensing by Immune System

Does Plasmid DNA act in a Common Immunological way of DNA Sensing?

DNA Sensing Machinery: Is there a Hope to Improve DNA Vaccine Immunogenicity in Humans?

Can DNA Plasmid Metabolites Be Adjuvant?




Chapter 12. Adjuvants Targeting the DNA Sensing Pathways – Alum Based Adjuvants

Understanding the Mechanisms of Action of Alum Through Vaccine Immunology

Recent Immunological Insights Into the Mechanisms of Action of Alum

Triggering of Innate Immune Signaling Following Alum-Adjuvanted Immunization

DNA Release and Signaling in the Adjuvant Activity of Alum

A Model for Self-DNA Induced Responses in Alum Immunization

Conclusions and Perspectives on the Role of Self-DNA Sensing in Vaccination


Chapter 13. Adjuvants Targeting the DNA Sensing Pathways – Cyclic-di-GMP and other Cyclic-Dinucleotides


Production and Functions of Cyclic-Dinucleotides in Bacteria

Production and Measurement of c-di-NMPS

Effects of c-di-NMPS on Cancer Cells

Effects of c-di-NMPS on Mammalian Innate Immune Responses

c-di-NMPS as Vaccine Adjuvants





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© Academic Press 2014
Academic Press
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About the Editor

Ken Ishii

Affiliations and Expertise

Vaccine Science Laboratory, Immunology Frontier Research Centre (IFReC), Osaka University, Japan

Choon Kit Tang

Affiliations and Expertise

Vaccine Science Laboratory, Malaria Immunology Laboratory, Host Defense Laboratory, Immunology Frontier Research Centre (IFReC), Osaka University, Osaka, Japan


"The overall themes are the discovery of double-stranded DNA immunogenicity and the definition of DNA sensing pathways, double-stranded DNA and its part in modulating human diseases, and the DNA sensing pathway and its impact on vaccinology.", April 2014

Ratings and Reviews