Activation and Evasion of Innate Immune Signaling Pathways by Yersinia Pestis PDF Download
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Author: Miqdad Onali Dhariwala
Publisher:
ISBN:
Category :
Languages : en
Pages : 153
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Book Description
The Gram-negative bacterial pathogen Yersinia pestis is the causative agent of plague, a rapidly lethal disease. The pathogen is transmitted by a flea vector and circulates in lower mammalian populations in the wild. Human beings are dead-end accidental hosts, however the pathogen is capable of human-to-human transmission, a trait responsible for 3 major pandemics in the past. The disease is characterized by an inflammation driven immunopathology accompanied by tissue necrosis and rapid bacterial proliferation. Our lab has previously demonstrated that the type I interferon (IFN), IFN-[beta] is a vital component of the inflammatory response that is utilized by the pathogen to advance disease. Despite a heavy involvement of inflammation, little is known about how the immune system detects the Y. pestis infection to initiate immune responses. In this work, we demonstrate that an intracellular form of Y. pestis is detected by an endosomal ssRNA sensor, Toll-like receptor 7 (TLR7). Traditionally viewed as a sensor of viral infections, we demonstrate here that Y. pestis depends on TLR7, not only to produce IFN-[beta], but also to cause disease. Furthermore, we demonstrate the existence of a non-canonical pathway leading to the secretion of this cytokine. This pathway does not involve the TLR7-adapter MyD88 but requires the TLR3, 4 adapter TRIF to produce IFN-[beta] and cause disease. We further show that this non-canonical pathway appears to lead to the activation of both NF[kappa]B and IRF3. Surprisingly, we also demonstrate an inability of Y. pestis to evade MyD88 in vivo, as MyD88-dependent immune responses were critical for secretion of protective cytokines like the type II IFN, IFN-[gamma]. From these results, we provide molecular insight into the host-pathogen interactions that lead to the development of plague.
Author: Miqdad Onali Dhariwala
Publisher:
ISBN:
Category :
Languages : en
Pages : 153
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Book Description
The Gram-negative bacterial pathogen Yersinia pestis is the causative agent of plague, a rapidly lethal disease. The pathogen is transmitted by a flea vector and circulates in lower mammalian populations in the wild. Human beings are dead-end accidental hosts, however the pathogen is capable of human-to-human transmission, a trait responsible for 3 major pandemics in the past. The disease is characterized by an inflammation driven immunopathology accompanied by tissue necrosis and rapid bacterial proliferation. Our lab has previously demonstrated that the type I interferon (IFN), IFN-[beta] is a vital component of the inflammatory response that is utilized by the pathogen to advance disease. Despite a heavy involvement of inflammation, little is known about how the immune system detects the Y. pestis infection to initiate immune responses. In this work, we demonstrate that an intracellular form of Y. pestis is detected by an endosomal ssRNA sensor, Toll-like receptor 7 (TLR7). Traditionally viewed as a sensor of viral infections, we demonstrate here that Y. pestis depends on TLR7, not only to produce IFN-[beta], but also to cause disease. Furthermore, we demonstrate the existence of a non-canonical pathway leading to the secretion of this cytokine. This pathway does not involve the TLR7-adapter MyD88 but requires the TLR3, 4 adapter TRIF to produce IFN-[beta] and cause disease. We further show that this non-canonical pathway appears to lead to the activation of both NF[kappa]B and IRF3. Surprisingly, we also demonstrate an inability of Y. pestis to evade MyD88 in vivo, as MyD88-dependent immune responses were critical for secretion of protective cytokines like the type II IFN, IFN-[gamma]. From these results, we provide molecular insight into the host-pathogen interactions that lead to the development of plague.
Author: Sanghita Sarkar
Publisher:
ISBN: 9781339085678
Category : Electronic dissertations
Languages : en
Pages : 286
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Book Description
Author: Justin Spinner
Publisher:
ISBN:
Category : Yersinia pestis
Languages : en
Pages : 284
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Book Description
The human innate immune system is reliant upon the coordinated activity of macrophages and polymorphonuclear leukocytes (neutrophils or PMNs) for recognition and elimination of invading pathogens. Yersinia spp. are renowned for their ability to subvert the innate immune system and cause disease in humans. Y. pestis, in particular, is a human pathogen of historical and current significance which relies on the activity of injected virulence plasmid encoded effector Yop proteins, via a type III secretion system, into host immune system cells to evade clearance by the immune system. The activity of Yops within murine macrophages and dendritic cells has been investigated; however, the activity of Yops within human polymorphonuclear leukocytes (neutrophils or PMNs) has not been directly examined. Herein, the coordinated activity of Y. pestis virulence plasmid encoded Yops on isolated human PMNs is explored. Specifically, the role of Yops in evasion of isolated human PMN phagocytosis, ROS production, killing, and induction of apoptosis is described. Y. pestis was found to inhibit isolated human PMN phagocytosis in a virulence plasmid dependent manner. However, a substantial number of Y. pestis are initially phagocytosed. Phagocytosed bacteria were killed by PMNs regardless of virulence plasmid dependent inhibition of reactive oxygen species (ROS) production, but there was a population of Y. pestis which survived inside the PMN independent of the presence of the virulence plasmid. Although Y. pestis inhibition of ROS did not directly impact the fate of intracellular bacteria, analysis of PMN cell death following incubation with virulence plasmid containing Y. pestis revealed that PMNs are not induced to undergo YopJ/YopP dependent caspase activation and apoptosis as in macrophages. The absence of the virulence plasmid actually resulted in greater PMN lysis following apoptosis. This suggests that, Yersinia ROS inhibition limits fulminate isolated human PMN apoptosis after phagocytosis.
Author: Isabella C. Felli
Publisher: Springer
ISBN: 3319201646
Category : Science
Languages : en
Pages : 428
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Book Description
This book discusses the paradigm-shifting phenomenon of intrinsically disordered proteins (IDPs) and hybrid proteins containing ordered domains and functional IDP regions (IDPRs). The properties of IDPs and IDPRs are highly complementary to those deriving from the presence of a unique and well-defined three-dimensional fold. Ignored for a long time in high-resolution studies of proteins, intrinsic protein disorder is now recognized as one of the key features for a large variety of cellular functions, where structural flexibility presents a functional advantage in terms of binding plasticity and promiscuity and this volume explores this exciting new research. Recent progress in the field has radically changed our perspective to study IDPs through NMR: increasingly complex IDPs can now be characterized, a wide range of observables can be determined reporting on the structural and dynamic properties, computational methods to describe the structure and dynamics are in continuous development and IDPs can be studied in environments as complex as whole cells. This volume communicates the new exciting possibilities offered by NMR and presents open questions to foster further developments. Intrinsically Disordered Proteins Studied by NMR Spectroscopy provides a snapshot to researchers entering the field as well as providing a current overview for more experienced scientists in related areas.
Author: Marina De Bernard
Publisher: Frontiers Media SA
ISBN: 2832520227
Category : Medical
Languages : en
Pages : 227
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Book Description
Author: Rodolphe Barrangou
Publisher: Springer Science & Business Media
ISBN: 364234657X
Category : Science
Languages : en
Pages : 300
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Book Description
CRISPR/Cas is a recently described defense system that protects bacteria and archaea against invasion by mobile genetic elements such as viruses and plasmids. A wide spectrum of distinct CRISPR/Cas systems has been identified in at least half of the available prokaryotic genomes. On-going structural and functional analyses have resulted in a far greater insight into the functions and possible applications of these systems, although many secrets remain to be discovered. In this book, experts summarize the state of the art in this exciting field.
Author: Richard T. Smith
Publisher: Elsevier
ISBN: 0323146260
Category : Nature
Languages : en
Pages : 553
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Book Description
Immune Surveillance deals with the issues regarding tumor immunology and surveillance, in which the central theme is all about the life span of the mammalian host that is depleted by the environment with mutagenic agents and solutions. The book is divided into six chapters. It includes discussions on the organization and modulation of cell membrane receptors, as well as the origin and expression of membrane antigens. It also covers the topics on the triggering mechanisms for and effector mechanisms activated by the cellular recognition. These topics analyze and evaluate alternatives for the recognition and destruction mechanisms in the knowledge of cell cooperation and requirements for immune recognition. A chapter provides discourse on a solution for the paradox of thriving tumors based on the demonstrable in vitro host immunity. Another discusses the generation of antibody diversity and the theory of self-tolerance. The last chapter explains the evaluation of the evidence for immune surveillance. This reference will be invaluable to those who specialize in immunology.
Author: Pedro Escoll
Publisher: Caister Academic Press Limited
ISBN: 9781910190692
Category : Medical
Languages : en
Pages : 0
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Book Description
Expert international authors critically review the most important current research in bacterial evasion of the host immune response. Topics range from an overview of the seven most important bacterial secretion systems to a thorough review of evsaion by mycobacteria. Essential reading for everyone involved in bacterial pathogenesis research.
Author: P.J. Sansonetti
Publisher: Springer Science & Business Media
ISBN: 3642772382
Category : Medical
Languages : en
Pages : 151
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Book Description
Shigellosis is present all over the world. Anyone traveling in developing countries knows that the control of this invasive disease of the intestine is a priority task for physicians and public health authorities. Victims are essentially young children, and complications such as the hemolytic uremic syndrome make shigellosis a systemic disease rather than simply an infection of the colonic mucosa. However, "Westerners" should not consider shigeJlosis as an unlikely threat of the tropics. The disease arises in industrialized countries as soon as breaches in sanitation appear. A few months ago, at least 500 people developed shigellosis in northern France in an outbreak of Shigella sonnei infection due to accidental contamination of an urban water delivery system. The pathogenesis of shigellosis is an extraordinary topic of research because study of the invasion of the colonic mucosa addresses fundamental questions on. the molecular and cellular mechanisms by which a bacterial pathogen can pene trate non phagocytic cells, survive, multiply, spread in the intra cellular compartment, and eventually kill host cells. Further development of the infection within subepithelial tissues as well as the mechanisms that contribute to the eradication of this process have barely been studied.
Author: Steffen Backert
Publisher: Springer
ISBN: 3319411713
Category : Medical
Languages : en
Pages : 288
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Book Description
This volume details our current understanding of the architecture and signaling capabilities of known canonical and non-canonical inflammasome complexes and highlights their action, in particular in response to infection with important bacterial model organisms and the corresponding disease pathologies. The first chapters review new insights into the assembly and structures of inflammasome components and emphasize general strategies of up- and downstream signaling events. In addition, the authors specifically discuss the composition and activity of inflammasomes during infection with various gut pathogens (Salmonella, Shigella, Yersinia, Listeria and Helicobacter), respiratory pathogens (Mycobacterium, Legionella, Burkholderia and Streptococcus) as well as skin and soft tissue pathogens (Francisella and Staphylococcus). The discoveries presented provide a better understanding of the cellular and molecular biology of inflammasomes, which will pinpoint important new therapeutic targets for the treatment and prevention of multiple infectious diseases in the future. It is a valuable resource for students, scientists and clinicians, providing up-to-date information on this emerging research topic.
