Download or read book Pharmacological Manipulation of Host Macrophage Responses to Mycobacterium Tuberculosis written by Mark Verway and published by . This book was released on 2015 with total page pages. Available in PDF, EPUB and Kindle. Book excerpt: "Mycobacterium tuberculosis (Mtb) latently infects ~2 billion people and active tuberculosis (TB) represents the leading cause of death from a curable disease. Cases of drug resistant tuberculosis have increased in recent years, driving the demand for new therapies. While antibiotics used for the treatment of tuberculosis target processes in Mtb which are critical for its replication and survival, host directed therapies (HDTs) have been suggested in recent years as possible adjunct therapies for the treatment of TB. The primary hypothesis of this thesis is that it is possible to change the host environment so as to make it unfavorable for the bacteria, thus limiting its capacity to replicate. In this thesis we examine two methods of manipulating the host response to infection to aid in the control of the bacteria, namely the use of vitamin D to modulate transcriptional responses and metformin to manipulate host metabolic responses. Although vitamin D deficiency is a common feature among patients presenting with active tuberculosis, the full scope of vitamin D action during Mtb infection is poorly understood. As macrophages are the primary site of Mtb infection and are sites of vitamin D signaling, we have used these cells to understand the molecular mechanisms underlying modulation of the immune response by the hormonal form of vitamin D, 1,25-dihydroxyvitamin D (1,25D). We found that the virulent Mtb strain H37Rv elicits a broad host transcriptional response. Transcriptome profiling also revealed that the profile of target genes regulated by 1,25D is substantially altered by infection, and that 1,25D generally boosts infection-stimulated cytokine/chemokine responses. We further focused on the role of 1,25D- and infection-induced interleukin 1[beta] (IL-1[beta]) expression in response to infection. 1,25D enhanced IL-1[beta] expression via a direct transcriptional mechanism. Secretion of IL-1[beta] from infected cells required the NLRP3/caspase-1 inflammasome. Due to the lack of conservation of this VDRE in mice, the impact of elevated IL-1[beta] production was investigated in a novel model wherein infected macrophages were co-cultured with primary human small airway epithelial cells. Co-culture significantly prolonged survival of infected macrophages, and 1,25D/infection-induced IL-1[beta] secretion from macrophages reduced mycobacterial burden by stimulating the anti-mycobacterial capacity of co-cultured lung epithelial cells. These effects were independent of 1,25D-stimulated autophagy in macrophages but dependent upon epithelial IL1R1 signaling and IL-1[beta]-driven epithelial production of the antimicrobial peptide DEFB4/HBD2. These data provide evidence that the anti-microbial actions of vitamin D extend beyond the macrophage by modulating paracrine signaling, reinforcing its role in innate immune regulation in humans. " --

Download or read book Immunoregulation of Host Macrophage Responses by Mycobacterium Tuberculosis written by Bin Ni and published by . This book was released on 2014 with total page pages. Available in PDF, EPUB and Kindle. Book excerpt: Rise in rates of multidrug-resistant and extensively drug-resistant tuberculosis indicate a dire need for new lines of therapies against novel targets. The results of these studies indicate that miRNAs, especially miR-132 and miR-26a, as well as MAPK pathways, including Tpl-2, may be excellent targets of host-directed therapies for tuberculosis and the knowledge gained here will benefit future studies to these ends.

Download or read book The Inflammasome written by Christine M. De Nardo and published by Humana. This book was released on 2013-07-13 with total page 0 pages. Available in PDF, EPUB and Kindle. Book excerpt: This Methods in Molecular Biology book offers methods for studying inflammasome function, including generation of inflammasome stimuli, monitoring of caspase-1 activity and processing, activation of IL-1β cytokines, plus lab protocols, material lists and tips.

Download or read book Nanotechnology Based Approaches for Tuberculosis Treatment written by Prashant Kesharwani and published by Academic Press. This book was released on 2020-06-10 with total page 284 pages. Available in PDF, EPUB and Kindle. Book excerpt: Nanotechnology Based Approaches for Tuberculosis Treatment discusses multiple nanotechnology-based approaches that may help overcome persisting limitations of conventional and traditional treatments. The book summarizes the types of nano drugs, their synthesis, formulation, characterization and applications, along with the most important administration routes. It also explores recent advances and achievements regarding therapeutic efficacy and provides possible future applications in this field. It will be a useful resource for investigators, pharmaceutical researchers, innovators and scientists working on technology advancements in the areas of targeted therapies, nano scale imaging systems, and diagnostic modalities in tuberculosis. Addresses the gap between nanomedicine late discovery and early development of tuberculosis therapeutics Explores tuberculosis nanomedicine standardization and characterization with newly developed treatment, diagnostic and treatment monitoring modalities Covers the field thoroughly, from the pathogenesis of tuberculosis and multi-drug resistant mycobacterium tuberculosis, to treatment approaches using nanotechnology and different nanocarriers

Download or read book The Mycobacterial Cell Envelope written by Mamadou Daffé and published by . This book was released on 2008 with total page 0 pages. Available in PDF, EPUB and Kindle. Book excerpt: Explains the unique characteristics that cause this large group of bacteria responsible for tuberculosis and leprosy to function differently; serves as a valuable reference for those working in the areas of biochemistry, genetics, genomics, and immunology.

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.

Download or read book Tuberculosis of the Central Nervous System written by Mehmet Turgut and published by Springer. This book was released on 2017-06-13 with total page 615 pages. Available in PDF, EPUB and Kindle. Book excerpt: Written and edited by leading international authorities in the field, this book provides an in-depth review of knowledge of tuberculosis of the central nervous system, with emphasis on clinical, diagnostics, and therapeutic features. Tuberculosis, one of the most lethal diseases in human history, still poses a serious threat in the world together with economic and social problems, although a great progress in the fight against this infectious disease in the last century. It covers the full range of tuberculosis of central nervous system and the chapters are organized into six sections: (1) the cranial; (2) the spinal; and (3) the peripheral portions of the nervous system; followed by (4) a section on the laboratory studies in tuberculosis; (5) a section on medical and surgical therapy; and (6) further insights into tuberculosis. This comprehensive reference book will be an ideal source for neurosurgeons, neurologists and specialists upon infectious diseases seeking both basic and more sophisticated information and surgical procedures relating to the complications associated with tuberculosis involving the spine, brain and peripheral nerves.

Download or read book Buruli Ulcer written by Gerd Pluschke and published by Springer. This book was released on 2019-04-29 with total page 287 pages. Available in PDF, EPUB and Kindle. Book excerpt: A major objective of this open access book is to summarize the current status of Buruli Ulcer (BU) research for the first time. It will identify gaps in our knowledge, stimulate research and support control of the disease by providing insight into approaches for surveillance, diagnosis, and treatment of Buruli Ulcer. Book chapters will cover the history, epidemiology diagnosis, treatment and disease burden of BU and provide insight into the microbiology, genomics, transmission and virulence of Mycobacterium ulcerans.

Download or read book Understanding Tuberculosis written by Pere-Joan Cardona and published by BoD – Books on Demand. This book was released on 2012-02-15 with total page 566 pages. Available in PDF, EPUB and Kindle. Book excerpt: Mycobacterium tuberculosis is a disease that is transmitted through aerosol. This is the reason why it is estimated that a third of humankind is already infected by Mycobacterium tuberculosis. The vast majority of the infected do not know about their status. Mycobacterium tuberculosis is a silent pathogen, causing no symptomatology at all during the infection. In addition, infected people cannot cause further infections. Unfortunately, an estimated 10 per cent of the infected population has the probability to develop the disease, making it very difficult to eradicate. Once in this stage, the bacilli can be transmitted to other persons and the development of clinical symptoms is very progressive. Therefore the diagnosis, especially the discrimination between infection and disease, is a real challenge. In this book, we present the experience of worldwide specialists on the diagnosis, along with its lights and shadows.

Download or read book Zinc Signaling in Physiology and Pathogenesis written by Toshiyuki Fukada and published by MDPI. This book was released on 2018-05-04 with total page 293 pages. Available in PDF, EPUB and Kindle. Book excerpt: This book is a printed edition of the Special Issue "Zinc Signaling in Physiology and Pathogenesis" that was published in IJMS

Download or read book Metformin written by Juber Akhtar and published by BoD – Books on Demand. This book was released on 2021-12-15 with total page 155 pages. Available in PDF, EPUB and Kindle. Book excerpt: Type 2 diabetes (T2D), also known as non-insulin-dependent diabetes mellitus (NIDDM), is a condition in which cells fail to respond to insulin properly. As the disease progresses, the body does not produce enough insulin. There are several classes of anti-diabetic medications available, including the oral agent metformin. This medication is recommended as first-line treatment for T2D, except for those patients with severe kidney or liver problems. This book discusses the molecular mechanism, pharmacokinetics, and uses of metformin, as well as presents information on adverse drug reactions, drug interactions, and the potential use of metformin in tuberculosis.

Download or read book The Mononuclear Phagocyte System in Infectious Disease written by Geanncarlo Lugo-Villarino and published by Frontiers Media SA. This book was released on 2019-10-04 with total page 790 pages. Available in PDF, EPUB and Kindle. Book excerpt: The Mononuclear Phagocyte System (MPS) of vertebrates is composed of monocytes, macrophages and dendritic cells. Together, they form part of the first line of immune defense against a variety of pathogens (bacteria, fungi, parasites and viruses), and thus play an important role in maintaining organism homeostasis. The mode of transmission, type of replication and mechanism of disease-causing differ significantly for each pathogen, eliciting a unique immune response in the host. Within this context, the MPS acts as both the sentinel and tailor of the immune system. As sentinels, MPS cells are found in blood and within tissues throughout the body to patrol against pathogenic insult. The strategy to detect 'microbial non-self' relies on MPS to recognize conserved microbial products known as 'pathogen-associated molecular pattern' (PAMPs). PAMPs recognition represents a checkpoint in the response to pathogens and relies on conserved 'pattern recognition receptors' (PRRs). Upon PRR engagement, MPS mount a cell-autonomous attack that includes the internalization and compartmentalization of intracellular pathogens into toxic compartments that promote destruction. In parallel, MPS cells launch an inflammatory response composed of a cellular arm and soluble factors to control extracellular pathogens. In cases when innate immunity fails to eliminate the invading microbe, MPS serves as a tailor to generate adaptive immunity for pathogen eradication and generation of "memory" cells, thus ensuring enhanced protection against re-infection. Indeed, MPS cell functions comprise the capture, process, migration and delivery of antigenic information to lymphoid organs, where type-1 immunity is tailored against intracellular microbes and type-2 immunity against extracellular pathogens. However, this potent adaptive immunity is also a double-edge sword that can cause aberrant inflammatory disorders, like autoimmunity or chronic inflammation. For this reason, MPS also tailors tolerance immunity against unwanted inflammation. Successful clearance of the microbe results in its destruction and proper collection of debris, resolution of inflammation and tissue healing for which MPS is essential. Reciprocally, as part of the evolutionary process taking place in all organisms, microbes evolved strategies to circumvent the actions bestowed by MPS cells. Multiple pathogens modulate the differentiation, maturation and activation programs of the MPS, as an efficient strategy to avoid a dedicated immune response. Among the most common evasion strategies are the subversion of phagocytosis, inhibition of PRR-mediated immunity, resistance to intracellular killing by reactive oxygen and nitrogen species, restriction of phagosome maturation, modulation of cellular metabolism and nutrient acquisition, regulation of cell death and autophagy, and modulation of pro-inflammatory responses and hijacking of tolerance mechanisms, among others. The tenet of this eBook is that a better understanding of MPS in infection will yield insights for development of therapeutics to enhance antimicrobial processes or dampen detrimental inflammation for the host's benefit. We believe that contributions to this topic will serve as a platform for discussion and debate about relevant issues and themes in this field. Our aim is to bring expert junior and senior scientists to address recent progress, highlight critical knowledge gaps, foment scientific exchange, and establish conceptual frameworks for future MPS investigation in the context of infectious disease.

Download or read book Fundamentals of Inflammation written by Charles N. Serhan and published by Cambridge University Press. This book was released on 2010-04-26 with total page 489 pages. Available in PDF, EPUB and Kindle. Book excerpt: The acute inflammatory response is the body's first system of alarm signals that are directed toward containment and elimination of microbial invaders. Uncontrolled inflammation has emerged as a pathophysiologic basis for many widely occurring diseases in the general population that were not initially known to be linked to the inflammatory response, including cardiovascular disease, asthma, arthritis, and cancer. To better manage treatment, diagnosis, and prevention of these wide-ranging diseases, multidisciplinary research efforts are underway in both academic and industry settings. This book provides an introduction to the cell types, chemical mediators, and general mechanisms of the host's first response to invasion. World-class experts from institutions around the world have written chapters for this introductory text. The text is presented as an introductory springboard for graduate students, medical scientists, and researchers from other disciplines wishing to gain an appreciation and working knowledge of current cellular and molecular mechanisms fundamental to inflammation.

Download or read book Tuberculosis Host Pathogen Interactions written by Jeffrey D. Cirillo and published by Springer Nature. This book was released on 2019-09-10 with total page 255 pages. Available in PDF, EPUB and Kindle. Book excerpt: This book summarizes the progress in studies of tuberculosis host-pathogen interactions from several perspectives: molecular microbiology, immunology, animal models, clinical studies, epidemiology, and drug discovery. Tuberculosis (TB) remains a severe global public health problem. Complex interactions between environmental, microbial and host factors lead to clinically relevant infections. Studies on bacterial virulence, host-genetic, and immunological factors contributing to the susceptibility to TB provide an ever-growing foundation of knowledge that is critical to finding new interventions. Studies of immune mechanisms against M. tuberculosis infection have identified immunological markers associated with specific phenotypes in the host, providing insight into how they may be used to augment current treatment strategies. Recent advances in diagnosis, therapeutics and vaccines, as well as basic-research oriented studies have shed light on the development of new directions for prevention, treatment and control of TB. Improved understanding of the interplay between the bacterium and host is a key component of reducing incidence worldwide.

Download or read book Lectin in Host Defense Against Microbial Infections written by Shie-Liang Hsieh and published by Springer Nature. This book was released on 2020-03-09 with total page 240 pages. Available in PDF, EPUB and Kindle. Book excerpt: This book systemically presents the latest research on lectins, covering all the major topics in the field, including the heterocomplex of lectins and Toll-like receptors, protective versus pathogenic functions in connection with microbial infections, and novel strategies for enhancing host immunity against infectious diseases caused by viruses, bacteria, and fungi. Lectins are a large group of glycan-binding proteins that recognize diverse glycan and non-glycan structures expressed on prokaryotic and eukaryotic cells, and are vital to cell-cell interactions, the attachment of microbes to host cells, and the recognition and activation of immune responses to exogenous and endogenous danger signals. The composition and structure of microbes are complex and include numerous ‘pathogen-associated molecular patterns’ or ‘damage-associated molecular patterns’. As such, microbes’ interactions with immune cells activate multiple innate immunity receptors and produce distinct inflammatory reactions, which can be protective to contain microbial invasion, or pathogenic to cause tissue damage and shock syndrome in the host. The book shares lessons learned from state-of-the art research in this field, highlights the latest discoveries, and provides insightful discussions on lectin-mediated inflammatory reactions, while also outlining future research directions.

Download or read book The New Paradigm of Immunity to Tuberculosis written by Maziar Divangahi and published by Springer Science & Business Media. This book was released on 2013-03-12 with total page 295 pages. Available in PDF, EPUB and Kindle. Book excerpt: This book illustrates the intimate relationship between alveolar macrophages and Mycobacterium tuberculosis (M.tb.), and the former’s role in both innate and adaptive immunity against M.tb. It covers research done over the last decade. It also explores the role of macrophage death following infection with M.tb. in determining whether successful immunity is stimulated, or whether clinical disease develops; furthermore, the function of host lipid mediators in macrophage death modality are addressed. The book also illustrates how the balance between prostaglandins and lipoxins determines whether infected macrophages undergo apoptosis or necrosis, which is the ultimate factor in the outcome of infection. Finally, it is a synthesis of the authors’ recent studies and the studies of others to offer a new understanding of immunity to tuberculosis.

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