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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 i… Read more
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Save up to 30% on top Physical Sciences & Engineering titles!
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.
Students, scientists and practitioners in innate immunology, autoimmune diseases and vaccinology
List of Contributors
Preface
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
Introduction
The Importance of the Innate Immune System
Endosomal-Membrane Bound DNA Sensor – TLR9
Cytosolic DNA Sensors
Conclusion
Acknowledgment
References
Chapter 2. The PYHIN Family of Molecules and their Functions Sensing dsDNA
Introduction
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
Conclusions
References
Chapter 3. Cytosolic DNA-Sensing and the STING Pathway
Introduction
The Toll-Like Pathway: TLR9 and CpG DNA
The STING Pathway and Intracellular DNA Signaling
STING and Inflammatory Disease
Other Sensors of Intracellular DNA
Conclusion
References
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
Conclusion
References
Section B: dsDNA and Its Part in Modulating Human Diseases
Chapter 5. Host DNA Induced Inflammation and Autoimmune Diseases
Introduction
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
References
Chapter 6. Toll-Like Receptor 9 and Toll-Like Receptor 7 in the Development and Regulation of Systemic Autoimmune Disease
Introduction
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
References
Chapter 7. Bacterial Infections and the DNA Sensing Pathway
Introduction
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
Conclusion
Acknowledgments
References
Chapter 8. Viral Infections and the DNA Sensing Pathway: Lessons from Herpesviruses and Beyond
Introduction
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
Acknowledgments
References
Chapter 9. Cancer Pathogenesis and DNA Sensing
IFN-Inducing Cytosolic DNA Sensors
Mediators of IFN-Inducing Cytosolic DNA Sensors
STING and TRIF Pathways
NF-κB
ProInflammatory Cytokines
Inflammasome-Inducing Cytosolic DNA Sensors
Conclusion
References
Chapter 10. DNA Damage Responses in Atherosclerosis
Background
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
Conclusion
Acknowledgment
References
Section C: The DNA Sensing Pathway and Its Impact on Vaccinology
Chapter 11. DNA Vaccine: Does it Target the Double Stranded-DNA Sensing Pathway?
Introduction
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?
Conclusions
Acknowledgments
References
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
References
Chapter 13. Adjuvants Targeting the DNA Sensing Pathways – Cyclic-di-GMP and other Cyclic-Dinucleotides
Introduction
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
Conclusions
References
Index
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