Sensing Dna In Antiviral Innate Immunity

The discovery of Toll-like receptors (TLRs) in the late 1990s ushered in a new age of discovery for innate immunity. The importance of TLRs for immunology and biomedical research was recognized with the Nobel Prize for Medicine or Physiology in 2011. The prize was shared by three scientists: Ralph Steinman (for the discovery of dendritic cells, whi

This Research Topic is the second volume of the “Community Series in Antiviral Innate Immune Sensing, Regulation, and Viral Immune Evasion”. Please see the first volume here. The innate immune system is crucial to defend against viruses or other pathogenic microbes in the early phases of infection. The response starts with detecting evolutionarily conserved structures, termed pathogen-associated molecular patterns (PAMPs), by a set of germline-encoded pattern-recognition receptors (PRRs). Following the detection of specific viral PAMPs, PRRs trigger the activation of intracellular signaling cascades, ultimately leading to the induction of type I interferons (IFNs), pro-inflammatory cytokines, and antiviral genes through the activation of interferon regulatory factor 3 (IRF3) and IRF7. Antiviral pathways need to be tightly regulated to ensure successful antiviral defenses and avoid aberrant or dysregulation of host immune signaling. We believe that the Research Topic will give updated insights into the dynamic fields of PAMPs sensing in antiviral innate immunity and viral immune evasion. We hope it will serve the purpose of encouraging new research. This Research Topic will provide an overall picture of antiviral innate immune sensing signal pathways, regulation, and viral immune evasion. We welcome the submission of Original Research, Review, Mini-Review, Hypothesis and Theory, and Perspective articles that cover, but are not limited to, the following subtopics:

This book explores methods to study the complex and evolving interplay between a virus and its host that range from model systems to the detection of chemical molecules. The collection starts with the application of humanized mice and zebrafish as model organisms to study virus-host interactions and induction of innate immune responses. Subsequent chapters outline diverse methods to detect small interfering RNAs, microRNAs, and virus-derived dsRNA from a variety of cells, tissues, and organisms, as well as to interrogating the cytosolic RNA and DNA sensing pathways, including using RNA PAMPs as molecular tools, purification of cGAMP from virus particles and infected cells, and mechanisms to visualize the subcellular localization and activation of the adaptor proteins MAVS and STING. Cutting-edge methods, including high-throughput and genome-wide CRISPR/Cas9 screens, chromosome conformation capture, and whole-exome sequencing, are described to identify novel mediators, pathways, and variants underlying host susceptibility. Given the importance of studying these pathways and players under physiologic conditions, methods describing the isolation of primary mouse sensory neurons and group 2 innate lymphoid cells are also provided. Finally, this collection comes full circle back to the whole organism level and concludes with epidemiological methods to investigate virus-host interactions and the induction of innate immunity. Written for the Methods in Molecular Biology series, chapters include introductions to their respective topics, lists of the necessary materials and reagents, step-by-step, readily reproducible laboratory protocols, and tips on troubleshooting and avoiding known pitfalls. Authoritative and practical, Innate Antiviral Immunity: Methods and Protocols spans a diverse array of approaches to study and elucidate the intricacies of this vital area of study. The chapter 'Morphological Separation of Clustered Nuclei in Histological Images' is published open access under a CC BY 4.0 license at link.springer.com.

The discovery of Toll-like receptors (TLRs) in the late 1990s ushered in a new age of discovery for innate immunity. The importance of TLRs for immunology and biomedical research was recognized with the Nobel Prize for Medicine or Physiology in 2011. The prize was shared by three scientists: Ralph Steinman (for the discovery of dendritic cells, which express TLRs and whose activation by them provides a link between innate and adaptive immunity), Jules Hoffman (who made the pioneering observation of Toll in fruit fly anti-fungal immunity) and Bruce Beutler (who uncovered the role of TLR4 in the response to LPS) Work on TLRs inspired many researchers, and led to a search for other receptors in innate immunity. There are now several additional families of such receptors known, notably RIG-I-like receptors (RLRs), C-type lectin receptors (CLRs) and AIM2-like receptors (ALRs) A notable feature is the detection of nucleic acids from pathogens, but also from host cells in certain contexts, particularly in autoimmune diseases.Nucleic Acid Sensors and Antiviral Immunity presents a timely and extensive account of the detection of nucleic acids in infection and inflammation. We have chapters by Beutler, Hoffman and Shizuo Akira, who is the most cited immunologist of the past ten years, for his work on innate immunity, which gives us an indication of the importance of the field. Several other pioneers in the field present comprehensive and highly lucid up-to-date accounts of their particular interests, revealing the large amount of activity in the past few years, as the literature continues to grow and become ever more complex. The fly yet again provides new insights, and anti-viral mechanisms in this key model organism are described. Other topics include the ability of viruses such as poxviruses, hepatitis C virus and HIV to interfere with detection and signalling; new insights into signalling including subcellular localization of signalling proteins, complex regulation of TLRs and RLRs by ubiquination and negative regulation by miRNAs; and the role of autophagy in antiviral defence. The importance of the RLRs in viral detection is widely reviewed. DNA sensing by ALRs and other receptors is extensively described, and the prospect of additional as yet unknown receptors for DNA debated, revealing a field that is still burgeoning. The prospect of therapeutic utility is covered in the context of using nucleic acids or other compounds as agents to promote anti-viral immunity.This book therefore represents an unprecedented account of this important aspect of immunology, by a stellar cast of authors who have defined the field. We have a key resource which should act as a primary source of information. The chapters will inspire researchers to continue on their quest to provide mechanistic insights into anti-viral innate immunity. The discoveries provide us with new strategies in the never ending war between humanity and viral infection, and will help in the ultimate goal to provide treatments to use against viruses which continue to present a major threat to human health.

Until recently, innate immunity was regarded as a relatively nonspecific system designed to engulf and destroy pathogens. However, new studies show that the innate immune system is highly developed in its ability to discriminate between self and foreign entities. Understanding this mechanism can lead to therapeutic strategies based on manipulation