Dna Sensors And Inflammasomes

DNA Sensors and Inflammasomes, Volume 625, the latest release in the Methods in Enzymology series, continues the legacy of this premier serial with quality chapters authored by leaders in the field. New sections in this release include Phosphorylation and dimerization of STING and IRF3, cGAS enzymology, Synthesis and identification of immuno-stimulatory CDNs, Tracking cGAS activity/ cGAMP formation using SPR/NMR, Using an enzyme coupled assay to track cGAS activity under steady states, Tracking the polymerization of DNA sensors, inflammasome receptors, and downstream signaling partners using FRET, NLRC4 structure, Tracking TREX1 activity, DNA association and dissociation kinetics of PARP1, and more. Provides the authority and expertise of leading contributors from an international board of authors Presents the latest release in the Methods in Enzymology series Includes the latest information on DNA sensors and inflammasomes

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.

The inflammasome was first described in 2002 as a molecular complex activating proinflammatory caspases and therefore regulating the maturation and biological activities of cytokines such as IL-1 and IL-18. This finding was substantiated by the identification of several mutations in the cias1 gene, encoding the human NLRP3 protein, responsible for several autoinflammatory disorders such as the Muckle Wells syndrome. Since, the interest for this complex has constantly increased and several inflammasome complexes with different specificities have been described. These inflammasomes sense a wide variety of pathogens and danger signals and are key players in the inflammatory response. With the contributions of leading international experts in the field, this book provides an extensive overview of the current knowledge of inflammasome biology and their role in health and disease.

Nucleic Acid Sensing and Immunity - PART A, Volume 344, provides a comprehensive overview of the nucleic acid machinery, from plants to mammalians, as well as their regulation. Specific chapters in this updated release include Molecular bases of discrimination between self from non-self nucleic acids, Intracellular RNA sensing in mammalian cells, Nuclear DNA damage and nucleic acid sensing, Negative regulation of nucleic acid sensing, Dendritic cell responses to exogenous nucleic acids, Activating the nucleic acid-sensing machinery for anticancer immunity, and Nucleic acid sensing and inflammasomes, amongst other topics. Provides an accurate, state-of-the-art resource on RNA sensing Includes the work of a well-known tumor immunologist Links intestinal host defense and viral nucleic acid sensing Presents a chapter on the negative regulation of DNA sensing, a timely topic

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

Nucleic Acid Sensing and Immunity - PART B, Volume 345 gives a comprehensive overview of the nucleic acid machinery, from plants to mammalians, along with their regulation. Chapters in this updated volume include Nucleic acids sensing in allergic disorders, Nucleic acids sensing in autoimmune disorders, Nucleic acid sensing in inflammatory disorders, Viral nucleic acid sensing inflammasomes in intestinal host defense, Genome damage sensing leads to tissue homeostasis in Drosophila, Nucleic acids sensing in plants, Nucleic Acid sensing in invertebrates, amongst other topics. Provides an accurate, state-of-the-art resource on RNA sensing Includes the work of a well-known tumor immunologist Links intestinal host defense and viral nucleic acid sensing Presents a chapter on the negative regulation of DNA sensing, a timely topic

Microbial double-stranded (ds)DNA potently stimulates innate immunity. Stimulator of interferon genes (STING) plays a major role in dsDNA-induced expression of type I interferons (IFNs) and elimination of invading pathogens. After stimulation, STING translocates from the endoplasmic reticulum to cytoplasmic punctate structures where it associates with TANK-binding kinase 1 (TBK1). TBK1 phosphorylates interferon regulatory factor 3 to induce type I IFNs and optineurin to induce autophagy, an intracellular clearance system. Autophagy-related protein, Atg9a, regulates membrane trafficking involved in STING movement and suppresses type I IFN expression. Absent in melanoma 2 (AIM2) plays a major role in dsDNA-induced inflammatory responses. After stimulation, AIM2 forms an inflammasome with an adaptor protein, ASC, and caspase-1, a protease, to induce the production of IL-1β, an inflammatory cytokine. Autophagy mediates degradation of activated AIM2-inflammasome to terminate the response. Thus, autophagy-related proteins, essential components of autophagy machinery, regulate innate immune responses induced by dsDNA.

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.

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.