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Book Regulation of Macrophage mediated Immunity to Influenza Virus Infection

Download or read book Regulation of Macrophage mediated Immunity to Influenza Virus Infection written by François Coulombe and published by . This book was released on 2015 with total page pages. Available in PDF, EPUB and Kindle. Book excerpt: "Influenza virus infection causes a complex respiratory disease inflicting a persistent threat to human health worldwide and presenting challenges to clinicians who are left with no available therapeutic interventions. The broad complexity of the disease is the consequence of host-pathogen interactions, which may result in severe influenza- associated illness and death. Severity of influenza infections correlates with the ability of the virus to reach and replicate within the lower respiratory tract, where it encounters alveolar macrophages. These cells reside in close contact with the respiratory epithelium of the lower airways and are the first immune cells to make contact with the influenza virus. Despite evidence showing their critical role in anti-viral immunity and in the maintenance of pulmonary homeostasis, the regulatory mechanisms that drive macrophage function during severe influenza virus infection are poorly defined.The first part of the work presented herein focuses on the function of host-derived lipid mediators, known as eicosanoids, in the regulation of macrophage function during influenza virus infection. Using mice deficient in various components of the eicosanoid biosynthesis pathways, we first established that influenza virus specifically hijacks the prostaglandin E2 pathway to subvert macrophage function and suppress both innate and adaptive immune responses. We identified two distinct pathways through which prostaglandin E2 paralyzed macrophage anti-viral immunity: type I interferon and apoptosis. The impairment of these two pathways severely hinders the innate immune response as type I interferon directly counteracts viral replication, while apoptosis blocks the cellular machinery crucial for viral amplification/dissemination. In addition, we found that prostaglandin E2 suppresses adaptive immunity to influenza virus infection. Importantly, prostaglandin E2-deficient mice were more protected against influenza and pharmacological inhibition of prostaglandin E2 recapitulated this protective effect against the virus.Next, we demonstrated that mice deficient in the 5-lipoxygenase pathway showed remarkable protection against influenza infection. This protection was associated with a concomitant lack of lipoxin A4 up-regulation in infected mice, as well as early expansion of granulocyte macrophage-colony stimulating factor (GM-CSF)-secreting alveolar macrophages in the airways. GM-CSF has a well-established protective role against pulmonary viral infection and specific inhibition of GM-CSF in 5-lipoxygenase deficient mice abrogated their protection against influenza.The second part of this thesis focuses on the consequences of macrophage death modality during the course of influenza virus infection. While host-induced apoptosis of infected cells is a mechanism to restrict viral replication, influenza virus paradoxically has been shown to induce early apoptosis in immune cells, especially in monocytes/macrophages, via its PB1-F2 accessory protein. Here, we demonstrate that the host NLRX1 receptor can effectively interact with the influenza virus pro-apoptotic protein PB1-F2 in macrophage mitochondria, thereby preventing PB1-F2-induced apoptosis and leading to increased type I interferon production by macrophages. The interaction between host NLRX1 and viral PB1-F2 in macrophages was furthermore critical for the control of influenza virus replication.Taken together, our results suggest that eicosanoids and apoptosis act in concert as critical regulators of macrophage-mediated immunity against severe influenza virus infection. We propose that macrophages act as the cellular switch initiating the pulmonary anti-viral responses by monitoring the balance between virus-triggered or host-triggered production of eicosanoids and induction of apoptosis. We further envision that immunotherapies targeting specific eicosanoids offer promising avenues for treatment of influenza and potentially other viral infections." --

Book Janeway s Immunobiology

    Book Details:
  • Author : Kenneth Murphy
  • Publisher : Garland Science
  • Release : 2010-06-22
  • ISBN : 9780815344575
  • Pages : pages

Download or read book Janeway s Immunobiology written by Kenneth Murphy and published by Garland Science. This book was released on 2010-06-22 with total page pages. Available in PDF, EPUB and Kindle. Book excerpt: The Janeway's Immunobiology CD-ROM, Immunobiology Interactive, is included with each book, and can be purchased separately. It contains animations and videos with voiceover narration, as well as the figures from the text for presentation purposes.

Book SARS  MERS and other Viral Lung Infections

Download or read book SARS MERS and other Viral Lung Infections written by David S. Hui and published by European Respiratory Society. This book was released on 2016-06-01 with total page 148 pages. Available in PDF, EPUB and Kindle. Book excerpt: Viral respiratory tract infections are important and common causes of morbidity and mortality worldwide. In the past two decades, several novel viral respiratory infections have emerged with epidemic potential that threaten global health security. This Monograph aims to provide an up-to-date and comprehensive overview of severe acute respiratory syndrome, Middle East respiratory syndrome and other viral respiratory infections, including seasonal influenza, avian influenza, respiratory syncytial virus and human rhinovirus, through six chapters written by authoritative experts from around the globe.

Book Mucosal Vaccines

    Book Details:
  • Author : Hiroshi Kiyono
  • Publisher : Elsevier
  • Release : 1996-10-23
  • ISBN : 0080537057
  • Pages : 501 pages

Download or read book Mucosal Vaccines written by Hiroshi Kiyono and published by Elsevier. This book was released on 1996-10-23 with total page 501 pages. Available in PDF, EPUB and Kindle. Book excerpt: This comprehensive, authoritative treatise covers all aspects of mucosal vaccines including their development, mechanisms of action, molecular/cellular aspects, and practical applications. The contributing authors and editors of this one-of-a-kind book are very well known in their respective fields. Mucosal Vaccines is organized in a unique format in which basic, clinical, and practical aspects of the mucosal immune system for vaccine development are described and discussed. This project is endorsed by the Society for Mucosal Immunology. Provides the latest views on mucosal vaccines Applies basic principles to the development of new vaccines Links basic, clinical, and practical aspects of mucosal vaccines to different infectious diseases Unique and user-friendly organization

Book Virus induced Immunopathology

Download or read book Virus induced Immunopathology written by Morris Pollard and published by . This book was released on 1968 with total page 322 pages. Available in PDF, EPUB and Kindle. Book excerpt:

Book The Innate Regulation of B 1 Lymphocyte Responses to Influenza Virus Infection

Download or read book The Innate Regulation of B 1 Lymphocyte Responses to Influenza Virus Infection written by Elizabeth Emlika Waffarn and published by . This book was released on 2014 with total page pages. Available in PDF, EPUB and Kindle. Book excerpt: Multiple B lymphocyte subsets contribute to immune responses to pathogens. Among these, B-1 cells are a small subset of innate-like B cells whose development, phenotype, tissue distribution, and functions are distinct from those of conventional B-2 cells, and whose responses are crucial to protection against mucosal bacterial and viral pathogens. B-1 cells contribute to protective responses even before infection, by secreting natural antibody, a polyspecific repertoire of mostly IgM antibodies produced constitutively in the absence of foreign antigens. In response to influenza virus infection, B-1 cells actively respond by accumulating locally in draining mediastinal lymph nodes (MedLN), where they differentiate to secrete both virus-binding and non virus-binding IgM. Multiple details from those earlier studies suggest that the regulation of B-1a cell responses differs from that of conventional B-2 cells and that infection-induced but antigen-independent mechanisms contribute to B-1a cell activation and function. This dissertation explores the hypothesis that B-1 cells are regulated by the quality and magnitude of local infection-induced innate immune signals, including type I interferon (IFNs) and IL-1, critical mediators of anti-viral responses and pro-inflammatory signaling. Previous studies of IL1R-/- mice showed that IL-1 signaling was required for maximal secretion of IgM and IgA after influenza infection. Because B-1 cells contribute at least half of influenza-induced IgM, we investigated the effects of IL-1 on B-1 cell redistribution and activation for IgM secretion. The studies outlined in the Second Chapter revealed that direct IL-1 stimulation did not contribute to the redistribution of B-1 cells to the lymph nodes, as it was neither directly chemotactic for B-1 cells, did not mobilize B-1 cells in vivo, nor altered the ability of B-1 cells to respond to the lymph node homing chemokines CXCL12 and CXCL13 in vitro. Instead, we found that IL-1 treatment alone modestly induced their IgM secretion in vitro. Using chimeric mice in which only B-1 cells lacked the IL-1R and which are distinguishable from B-2 cells based on Ig-allotypic differences, we investigated the ability of B-1 cells to respond to influenza virus infection. The data showed that these signals were required for maximum induction not only of CD5- B-1 cells, but also of the mostly B-2 cell-derived plasma blasts. Consistent with these findings we found IgM production both by B-1 and B-2 cells reduced. To begin to determine the mechanism by which B-1 cell IL-1 stimulation causes B-2 cell differentiation, we found that IL-1 stimulation selectively induced GM-CSF stimulation by B-1 cells. Furthermore, supernatants of IL-1-stimulated B-1 cells were able to induce IgM secretion by B-2 cells in vitro. Together, these findings suggest that activated B-1 cells play a regulatory role within lymph nodes by guiding conventional B-2 cell responses. In the Third Chapter, we took a genome-wide gene expression array approach to conduct an unbiased analysis of B-1a cell populations in the peritoneal and pleural cavity and the spleen, before and at two time points after infection. The goal was to identify all signals that affect B-1a cells following influenza infection in vivo and to identify a likely source from which lymph node B-1 cells were recruited. Somewhat surprisingly, the results revealed strong gene expression differences present before infection between B-1 cells from different tissues. Influenza virus infection further altered gene expression from all three sites, but the strongest changes occurred in pleural cavity B-1a cells within 2 days of infection, indicating that rapidly induced, locally elaborated infection signals impact B-1a cells. Based on the affected genes, type I IFN was identified as a strong early innate factor providing site-specific signaling to B-1a cells. These results suggest that B-1a cells receive site-specific signals even prior to infection and that infection-induced local signals strongly affect pleural cavity B-1a cells, likely shaping their antiviral response. The Fourth Chapter investigates the tissue origins of B-1a cells accumulating at the site of influenza infection and the role of type I IFN in their migration and differentiation. Labeled B-1a cells preferentially redistributed from pleural cavity sites to the draining MedLN after influenza infection, consistent with the results of our microarray analyses. However, in mice in which only B cells, or only B-1 cells lacked IFNR-expression, this enhanced accumulation was absent suggesting a role for type I IFN signaling B-1 cell redistribution. An in vitro vascular mimetic chamber model was used to evaluate the adherence of B-1 cells to a substrate consisting of ICAM-1 and CXCL13. Strikingly, type I IFN treatment or in vivo influenza infection stimulated B-1 cells to arrest on the substrate. Antibody-blocking studies showed that this was due to the increased integrin-mediated binding to ICAM-1. In vivo competition experiments designed to measure the ability of B-1 cells, from wildtype and CD11b or CD11a integrin-deficient mice, to accumulate in the MedLN in response to influenza infection after transfer into the pleural cavity of recipient mice, demonstrated the importance of CD11b in the B-1 cell redistribution process. Further studies suggested that type I IFN acts to enhance CD11b-mediated lymph node accumulation by activating the conformation state of CD11b. These studies identify a novel axis of type I IFN mediated integrin activation for rapid regulation of innate lymphocyte redirection. Together, these studies provide two examples of innate-signaling mediated regulation of B-1 cell responses during influenza infection. The results indicate that B-1 cells in the body cavities are optimally positioned to rapidly respond to an infection and that their characteristic expression of CD11b aids in rapid migration and accumulation in regional lymphoid tissues. Finally, the results of this study also suggest that B-1a cells broadly regulate the adaptive antiviral response by providing non-redundant signals to conventional B-2 cells for maximal induction of virus-specific antibody responses.

Book Cell Mediated Immune Response to Influenza Virus Infection

Download or read book Cell Mediated Immune Response to Influenza Virus Infection written by Nai Ki Mak and published by . This book was released on 1983 with total page 456 pages. Available in PDF, EPUB and Kindle. Book excerpt:

Book Persistent Viral Infections

Download or read book Persistent Viral Infections written by R. Ahmed and published by Wiley-Blackwell. This book was released on 1999 with total page 754 pages. Available in PDF, EPUB and Kindle. Book excerpt: Persistent Viral Infections Edited by Rafi Ahmed Emory Vaccine Center, Atlanta, USA and Irvin S. Y. Chen UCLA School of Medicine, Los Angeles, USA During the past decade much of our attention has focused on diseases associated with viral persistence. Major breakthroughs in immunology, and the advent of molecular approaches to study pathogenesis have increased our understanding of the complex virus-host interactions that occur during viral persistence. Persistent Viral Infections focuses on: * The pathogenesis and immunology of chronic infections * Animal models that provide, or have the potential to provide, major insights This volume will be essential reading for virologists, immunologists, oncologists and neurologists.

Book The State of T Cell Immunity Against Influenza Virus in Humans and Exploration of Potential Strategies to Enhance Cell Mediated Protection from Influenza Infection

Download or read book The State of T Cell Immunity Against Influenza Virus in Humans and Exploration of Potential Strategies to Enhance Cell Mediated Protection from Influenza Infection written by Lisa Wagar and published by . This book was released on 2013 with total page pages. Available in PDF, EPUB and Kindle. Book excerpt:

Book The Role of Nrf2 Activation on the Murine T Cell Response to Influenza Infection

Download or read book The Role of Nrf2 Activation on the Murine T Cell Response to Influenza Infection written by Robert Arthur Freeborn (III) and published by . This book was released on 2020 with total page 226 pages. Available in PDF, EPUB and Kindle. Book excerpt: Influenza infections cause millions of hospitalizations globally each year, resulting in hundreds of thousands of deaths and exacting a large toll on the economy. Accordingly, new interventions are highly desired including the elusive universal influenza vaccine capable of providing long-lasting immunity to all strains of influenza, including those which have not yet circulated in humans. It is vital to determine factors which suppress immunity to influenza infection and worsen host outcomes during infection. The food additive, tert-butylhydroquinone (tBHQ), was shown by our lab to modulate CD4+ T cell activation and function in ex vivo analyses, in part by activating the stress-activated transcription factor, nuclear factor erythroid 2-related factor 2 (Nrf2). However, it was unknown if tBHQ hindered T cell function in vivo. To assess this, we fed mice diets with or without 0.0014% tBHQ and infected them with sublethal influenza A virus. Following primary infection, mice exposed to tBHQ had fewer CD8+ T cells in the lungs, and these cells displayed a phenotype consistent with reduced effector function. Notably, these findings correlated with augmented viral RNA levels in the lungs. Following secondary infection with a heterosubtypic strain of influenza virus, mice on tBHQ-containing diets had exacerbated weight loss and delayed recovery compared to mice on control diets, indicating that tBHQ impaired heterosubtypic memory responses. It was further revealed that splenic memory T cell populations were diminished 28 days following primary infection in mice on the tBHQ diet, suggesting failure to form a memory T cell population could be the cause for the diminished heterosubtypic immunity. To begin elucidating the molecular mechanism by which tBHQ suppressed the T cell response to influenza infection, two different models were utilized. The first model used adoptive transfer of wildtype or Nrf2-null T cells into T cell-deficient hosts prior to dietary exposure to tBHQ and infection with influenza virus. Interestingly, tBHQ had no effect on wildtype T cells in this model. However, this model demonstrated that Nrf2 in T cells contributes to influenza-associated morbidity, as mice with Nrf2-deficient T cells had reduced lung damage and ultimately lost less weight than their control counterparts. The other model exploited Cre/Lox technology to generate a conditional knockout mouse line with Nrf2-deficient T cells. In this model, the effects of tBHQ seen in wildtype mice during primary infection were shown to require Nrf2 in T cells. Additionally, this model also showed that mice with Nrf2-deficient T cells were protected from influenza-associated morbidity, though this only occurred in the presence of tBHQ. These studies collectively show that Nrf2 modulates the T cell response to influenza virus and contributes to host morbidity. Additionally, Nrf2 activation by tBHQ suppresses T cell responses to infection leading to failed memory responses. These are the first studies to investigate the role of tBHQ on T cellmediated immunity in vivo in addition to interrogating the role of Nrf2 in T cell responses to influenza virus infection.

Book T Cell Mediated Immunity to Influenza in Humans

Download or read book T Cell Mediated Immunity to Influenza in Humans written by Laurel Yong-Hwa Lee and published by . This book was released on 2008 with total page pages. Available in PDF, EPUB and Kindle. Book excerpt:

Book Influenza Pathogenesis and Control   Volume I

Download or read book Influenza Pathogenesis and Control Volume I written by Richard W. Compans and published by Springer. This book was released on 2014-10-08 with total page 442 pages. Available in PDF, EPUB and Kindle. Book excerpt: This two-volume work covers the molecular and cell biology, genetics and evolution of influenza viruses, the pathogenesis of infection, resultant host innate and adaptive immune response, prevention of infection through vaccination and approaches to the therapeutic control of infection.. Experts at the forefront of these areas provide critical assessments with regard to influenza virology, immunology, cell and molecular biology, and pathogenesis. Volume I provides overviews of the latest findings on molecular determinants of viral pathogenicity, virus entry and cell tropism, pandemic risk assessment, transmission and pathogenesis in animal species, viral evolution, ecology and antigenic variation, while Volume II focuses on the role of innate and adaptive immunity in pathogenesis, development of vaccines and antivirals.

Book Molecular Biology of The Cell

Download or read book Molecular Biology of The Cell written by Bruce Alberts and published by . This book was released on 2002 with total page 0 pages. Available in PDF, EPUB and Kindle. Book excerpt:

Book Trained Immunity based Vaccines

Download or read book Trained Immunity based Vaccines written by Jose Luis Subiza and published by Frontiers Media SA. This book was released on 2021-08-25 with total page 195 pages. Available in PDF, EPUB and Kindle. Book excerpt: Dr. Jose Luis Subiza is the founder and CEO of Inmunotek SL. The other Topic Editors declare no competing interests with regard to the Research Topic subject.

Book Infectious Disease Epidemiology

Download or read book Infectious Disease Epidemiology written by Ibrahim Abubakar and published by Oxford University Press. This book was released on 2016-04-07 with total page 295 pages. Available in PDF, EPUB and Kindle. Book excerpt: Infectious Disease Epidemiology is a concise reference guide which provides trainees and practicing epidemiologists with the information that they need to understand the basic concepts necessary for working in this specialist area. Divided into two sections, part one comprehensively covers the basic principles and methods relevant to the study of infectious disease epidemiology. It is organised in order of increasing complexity, ranging from a general introduction to subjects such as mathematical modelling and sero-epidemiology. Part two examines key major infectious diseases that are of global significance. Grouped by their route of transmission for ease of reference, they include diseases that present a particular burden or a high potential for causing mortality. This practical guide will be essential reading for postgraduate students in infectious disease epidemiology, health protection trainees, and practicing epidemiologists.