Author: Cheryl Lynn Birmingham Publisher: ISBN: 9780494447727 Category : Cytology Languages : en Pages : 388
Book Description
Autophagy is a cytosolic degradation pathway responsible for delivering proteins and organelles to the lysosome for degradation. Recently, this pathway has been shown to be an important component of innate immunity. In this thesis, I study two intracellular pathogens with very different lifestyles and compare how they interact with autophagy. Salmonella enterica serovar Typhimurium is a vacuole-adapted pathogen that replicates in the Salmonella -containing vacuole (SCV) in host cells. During in vitro infection of epithelial cells, a population of bacteria damages the SCV and replicates in the cytosol. I show here that bacteria in damaged SCVs are targeted by autophagy. This serves to protect the cytosol from bacterial colonization and restricts bacterial replication in this cell-type. Furthermore, damage to the SCV membrane appears to act as a signal to recruit autophagy. Listeria monocytogenes is a cytosol-adapted pathogen that lyses the phagosome and replicates in the cytosol. Listeriolysin O (LLO) and bacterial phospholipases C (PLCs) form pores in the phagosomal membrane to mediate this escape. Once in the cytosol, L. monocytogenes expresses ActA to mediate actin-based motility and intercellular spread. In macrophages, a significant population of bacteria is targeted by autophagy during phagosomal escape in an LLO-dependent manner. However, once in the cytosol, L. monocytogenes is able to evade autophagy. ActA is sufficient but not necessary for autophagy evasion. Accordingly, bacterial PLCs also play a role in autophagy evasion. During infection of macrophages, we observed that a small population of L. monocytogenes replicates in Spacious Listeria -containing Phagosomes (SLAPs). LLO is essential for SLAP formation and inhibits the maturation of these compartments by forming pores in the SLAP membrane. Furthermore, we found that impaired LLO expression allows slow bacterial replication in vacuoles in an autophagy-dependent manner. Therefore, SLAPs appear to represent a 'stalemate' between bacterial virulence (LLO activity) and host innate immunity (autophagy). SLAP-like structures were observed during persistent L. monocytogenes infection of immuno-deficient mice. This work provides insights into signals that target autophagy to intracellular pathogens and mechanisms by which pathogens have evolved to evade this innate immune mechanism. Furthermore, this research suggests a possible mechanism for the establishment of persistent infection.
Author: Beth Levine Publisher: Springer Science & Business Media ISBN: 3642003028 Category : Medical Languages : en Pages : 345
Book Description
Autophagy is a fundamental biological process that enables cells to autodigest their own cytosol during starvation and other forms of stress. It has a growing spectrum of acknowledged roles in immunity, aging, development, neurodegeneration, and cancer biology. An immunological role of autophagy was first recognized with the discovery of autophagy’s ability to sanitize the cellular interior by killing intracellular microbes. Since then, the repertoire of autophagy’s roles in immunity has been vastly expanded to include a diverse but interconnected portfolio of regulatory and effector functions. Autophagy is an effector of Th1/Th2 polarization; it fuels MHC II presentation of cytosolic (self and microbial) antigens; it shapes central tolerance; it affects B and T cell homeostasis; it acts both as an effector and a regulator of Toll-like receptor and other innate immunity receptor signaling; and it may help ward off chronic inflammatory disease in humans. With such a multitude of innate and adaptive immunity functions, the study of autophagy in immunity is one of the most rapidly growing fields of contemporary immunological research. This book introduces the reader to the fundamentals of autophagy, guides a novice and the well-informed reader alike through different immunological aspects of autophagy as well as the countermeasures used by highly adapted pathogens to fight autophagy, and provides the expert with the latest, up-to-date information on the specifics of the leading edge of autophagy research in infection and immunity.
Author: William T. Jackson Publisher: John Wiley & Sons ISBN: 1118677641 Category : Science Languages : en Pages : 364
Book Description
The relationship between infection and immunity and autophagy, a pathway of cellular homeostasis and stress response, has been a rapidly growing field of study over the last decade. While some cellular processes are pro- or anti-infection, autophagy has been proven to be both: a part of the innate immune response against some microbes, and a cellular pathway subverted by some pathogens to promote their own replication. Autophagy, Infection, and the Immune Response provides a unified overview of the roles of cellular autophagy during microbial infection. Introductory chapters ground the reader by delineating the autophagic pathway from a cellular perspective, and by listing assays available for measuring autophagy. Subsequent chapters address virus interactions with autophagy machinery, the various roles of autophagy parasitic infection, and interactions of bacteria with the autophagic pathway. Concluding chapters explore the relationships of autophagy to systemic immune responses, including antigen presentation, ER stress, and production of IFN-gamma. Designed as a resource for those interested in initiating studies on the relationship between autophagy and infection or immunity, Autophagy, Infection, and the Immune Response combines practical state-of the art technique descriptions with an overview of the wide variety of known interactions between pathogens and the autophagic pathway.
Author: Jun Cui Publisher: Springer Nature ISBN: 981150606X Category : Medical Languages : en Pages : 203
Book Description
This book discusses novel concepts and discoveries concerning the regulation of innate immunity by autophagy and autophagy-related proteins. In the past decade, there have been major advances in our understanding of the molecular mechanisms of autophagy and its physiological functions. This book highlights emerging studies on the underlying mechanisms of autophagy regulation of innate immunity, including inflammation, antiviral immunity and anti-bacterial responses and the signaling pathways that prompt or inhibit the initiation and progression of related diseases. It also offers new ideas and strategies for future drugs based on manipulating autophagy, especially selective autophagy mediated by cargo receptors. Providing a comprehensive overview of the autophagy regulation of innate immunity, it is a valuable resource for graduate students and researchers in the fields of immunology, cell biology and translational medicine.
Author: Vojo Deretic Publisher: John Wiley & Sons ISBN: 3527608540 Category : Science Languages : en Pages : 286
Book Description
This first book to cover this new topic at the interface of cell biology, immunology and infection biology offers a unique insight as to how the innate and possibly the adaptive immune system are shaped by cellular mechanisms. Following a comprehensive introduction to autophagy, the work features cellular mechanisms and medical implications, structured according to all major pathogens, while also covering emerging infectious diseases, such as tuberculosis. Edited by one of the authors of a groundbreaking paper on this topic.
Author: M. A. Hayat Publisher: Academic Press ISBN: 0128094273 Category : Medical Languages : en Pages : 431
Book Description
Autophagy: Cancer, Other Pathologies, Inflammation, Immunity, Infection, and Aging is an eleven volume series that discusses in detail all aspects of autophagy machinery in the context of health, cancer, and other pathologies. Autophagy maintains homeostasis during starvation or stress conditions by balancing the synthesis of cellular components and their deregulation by autophagy. This series discusses the characterization of autophagosome-enriched vaccines and its efficacy in cancer immunotherapy. Autophagy serves to maintain healthy cells, tissues, and organs, but also promotes cancer survival and growth of established tumors. Impaired or deregulated autophagy can also contribute to disease pathogenesis. Understanding the importance and necessity of the role of autophagy in health and disease is vital for the studies of cancer, aging, neurodegeneration, immunology, and infectious diseases. Comprehensive and forward-thinking, these books offer a valuable guide to cellular processes while also inciting researchers to explore their potentially important connections. Presents the most advanced information regarding the role of the autophagic system in life and death Examines whether autophagy acts fundamentally as a cell survivor or cell death pathway or both Introduces new, more effective therapeutic strategies in the development of targeted drugs and programmed cell death, providing information that will aid in preventing detrimental inflammation Features recent advancements in the molecular mechanisms underlying a large number of genetic and epigenetic diseases and abnormalities, including atherosclerosis and CNS tumors, and their development and treatment Includes chapters authored by leaders in the field around the globe—the broadest, most expert coverage available
Author: Roberta A. Gottlieb Publisher: Academic Press ISBN: 0123851025 Category : Medical Languages : en Pages : 241
Book Description
Autophagy in Health and Disease offers an overview of the latest research in autophagy with a translational emphasis. This publication takes scientific research in autophagy a step further and offers integrated content with advancements in autophagy from cell biology and biochemical research to clinical treatments. A necessary reference for the bookshelf of medical and scientific researchers and students, Autophagy in Health and Disease presents high quality, reputable information on autophagy, allowing the reader quick access to the most applicable information. Discusses current understanding of the roles of autophagy in health and disease Covers the background of autophagy, the development of tools and therapeutics to measure and modulate autophagy, and autophagy in tissues and disease processes
Author: Maria Chiara Maiuri Publisher: Springer ISBN: 3319300792 Category : Medical Languages : en Pages : 409
Book Description
Autophagy principally serves an adaptive function to protect organisms against diverse human pathologies, including cancer and neurodegeneration. Recent developments using in vitro, ex vivo and in vivo models show the involvement of the autophagy pathway in immunity and inflammation. Moreover, direct interactions between autophagy proteins and immune signalling molecules have also been demonstrated. Defects in autophagy - similar to cancer, neurodegenerative diseases and aging - through autophagy gene mutation and/or microbial antagonism, may underlie the pathogenesis of many infectious diseases and inflammatory syndromes. In spite of the increasing awareness of the importance of autophagy in these pathophysiological conditions, this process remains underestimated and is often overlooked. As a consequence, its role in the initiation, stability, maintenance, and progression of these diseases are still poorly understood. This book reviews the recent advances regarding the functions of the autophagy pathway and autophagy proteins in immunity and inflammation, focusing on their role in self-nonself distinction, their implications in innate and adaptive immune responses and their dysregulation in the pathology of certain inflammatory and autoimmune diseases.
Author: Daniel A. Escobar Publisher: Elsevier Inc. Chapters ISBN: 0128069430 Category : Medical Languages : en Pages : 40
Book Description
In this chapter we discuss sepsis-induced inflammation and organ dysfunction, as well as the role of autophagy as a protective cell signaling mechanism. Sepsis is a leading cause of death worldwide, and is the most common precipitant of organ dysfunction. It has been noted that a minimal amount of cell death is present in patients who succumb to sepsis-induced organ failure and that, after the septic insult has passed, organs have the potential to regain function, suggesting a hibernating state of the cell in order to protect it from apoptosis and death. The cellular and molecular processes involved in sepsis are complex, and continue to be elucidated. Autophagy has been extensively studied in recent decades and an exponential increase in knowledge regarding this physiological pathway used by cells has been found. It is known to be activated under stress conditions in order to protect the cell from dying. In the setting of sepsis it has been demonstrated to play an important role for recycling of unhealthy mitochondria and damaged organelles, thus decreasing injury by ROS and providing nutrients and amino acids that the cell can use in this stressful environment. The purpose of this chapter is to review what is known about autophagy in sepsis and describe the contributing mechanisms by which autophagy can protect against organ injury.
Author: Cheryl Lynn Birmingham
Author: Chinnaswamy Jagannath
Author: Beth Levine
Author: William T. Jackson
Author: Jun Cui
Author: Vojo Deretic
Author: M. A. Hayat
Author: Roberta A. Gottlieb
Author: Maria Chiara Maiuri
Author: Daniel A. Escobar