Biological Dna Sensor

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. 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

In this chapter, we reflect on our early understanding of the immunogenic properties of dsDNA and give a chronological account of the journey we have taken to discover the individual cellular DNA sensors which have played important roles in mediating DNA induced inflammation.

Toll-like receptors, NOD-like receptors and numerous intracellular sensors that detect nucleotides in the cytosol help to initiate immune responses to viral infections. Many of the cytosolic nucleotide sensors and their downstream mediators also play a role in RNA metabolism, DNA repair and cancer. Here we review the evidence that links cytosolic DNA sensors to processes that are activated in cancer cells.

The innate immune response serves as the first line of defense against microbial infections by detecting pathogen-associated molecular patterns through germline-encoded pattern recognition receptors. Proteins of the PYHIN family have gained substantial research focus in recent years as central mediators of innate immune responses induced by cytosolic microbial DNA. Sensing of DNA by PYHINs typically leads to activation of inflammasomes and/or type I interferon responses that are crucial for host defense against invading pathogens. Certain members of the family are also involved in the development of autoimmune diseases as well as transcriptional regulation. Although the generation of knockout mice strains has unraveled the essential role of PYHIN proteins such as AIM2 in the development of antimicrobial innate immune responses, the exact biological role of several other PYHIN family members remains to be understood. This chapter reviews the important discoveries on PYHIN proteins and their role in microbial defense, autoimmunity and transcriptional regulation.

Aluminum-based adjuvants (alum) are among the oldest and most widely used vaccine adjuvants. After decades of largely empirical use, the last years have witnessed a flurry of studies aiming to decipher the immunological mechanisms of action of alum. Along with other hypotheses, recent reports support that alum induces the release by host cells of their own DNA at sites of injection. Extracellular self-DNA would in turn activate the innate immune system through known and yet to be identified innate immune pathways and in this way boost the adaptive response to vaccine antigens. This chapter discusses the evidence supporting the view of self-DNA as a damage-associated molecular pattern implicated in the adjuvant activity of alum, its possible links with other proposed mechanisms, as well as future directions in the area of the sensing of self-nucleic acids in the modulation of immunological responses to vaccines.

The detection of bacterial pathogens by the innate immune system is mediated by various pattern recognition receptors that sense microbial molecules such as cell wall components, virulence factors or nucleic acids. Bacterial DNA is recognized by Toll-like receptor 9 (TLR9) at endosomal compartments and by cyclic GMP-AMP synthase, polymerase III/RIG-I, AIM2-like receptors (ALRs), DNA helicases as well as other incompletely characterized proteins in the host cell cytosol. Depending on the receptor and specific engagement of the adapter molecules MyD88, STING, MAVS or ASC, sensing of bacterial DNA triggers expression of NF-κB-dependent proinflammatory genes, type I IFN responses, and/or inflammasome activation. Whereas inflammatory gene expression and inflammasome activation are required for an effective host defense to most bacterial infections, type I IFNs appear to play a regulatory role and can be beneficial or detrimental for the host. This chapter summarizes the current knowledge about the mechanisms of DNA sensing and its function in bacterial infections.

DNA sensors initiate innate immune responses upon recognition of microbial and self-derived DNA in the intracellular compartments or cytoplasm. These sensors include TLR9, AIM2 like receptors and many other recently identified cytosolic DNA sensors. The otherwise protective nature of host defense by these receptors can turn hostile when they recognize self-DNA through various mechanisms and aberrantly activate DNA sensing pathways leading to unregulated or inappropriate type I IFN production and consequent autoimmune and autoinflammatory diseases. In this chapter, we highlight the current findings that shed light on the complex initiator and effector mechanisms that contribute to autoimmune disease pathology, including DNA sensing receptors, self and non-self discrimination, type I IFN system, mechanisms of enhanced self-DNA access to TLR9 and defective host DNA clearance.

Applications of nucleic acids have developed recently to provide solutions for biosensors, diagnostic tools and as platforms for the assembly of complex structures. These developments have been possible as their base sequence can be used to assemble precise structures following simple and predictable rules. Self-assembled DNA can then be amplified using polymerase chain reaction (PCR) and this ultimately enables the preparation of synthetic nucleic acids. Their use as molecular tools or DNA-conjugates has recently been enhanced by the addition of other groups including enzymes, fluorophores and small molecules. Written by leaders in the field, this volume describes the preparation and application of these DNA-conjugates. Several have been used as sensors (aptamers, riboswitches and nanostructures) based on the ability of nucleic acids to adopt specific structures in the presence of ligands, whilst others link reporter groups such as proteins or fluorophores to RNA or DNA for detection, single molecule studies, and increasing the sensitivity of PCR. The book is relevant to researchers in areas related to analytical chemistry, chemical biology, medicinal chemistry, molecular pharmacology, and structural and molecular biology.