Author: Mark Verway Publisher: ISBN: Category : Languages : en Pages :
Book Description
"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. " --
Author: Bin Ni Publisher: ISBN: Category : Languages : en Pages :
Book Description
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.
Author: Christine M. De Nardo Publisher: Humana ISBN: 9781627035224 Category : Medical Languages : en Pages : 0
Book Description
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.
Author: Mamadou Daffé Publisher: ISBN: 9781555814687 Category : Bacterial cell walls Languages : en Pages : 0
Book Description
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.
Author: Geanncarlo Lugo-Villarino Publisher: Frontiers Media SA ISBN: 2889630579 Category : Languages : en Pages : 790
Book Description
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.
Author: Prashant Kesharwani Publisher: Academic Press ISBN: 0128226110 Category : Business & Economics Languages : en Pages : 284
Book Description
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
Author: Kenneth Murphy Publisher: Garland Science ISBN: 9780815344575 Category : Medical Languages : en Pages :
Book Description
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.
Author: Gerd Pluschke Publisher: Springer ISBN: 3030111148 Category : Medical Languages : en Pages : 287
Book Description
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.
Author: Mehmet Turgut Publisher: Springer ISBN: 3319507125 Category : Medical Languages : en Pages : 615
Book Description
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.
Author: Pere-Joan Cardona Publisher: BoD – Books on Demand ISBN: 953307938X Category : Medical Languages : en Pages : 566
Book Description
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.
Author: Mark Verway
Author: Bin Ni
Author: Christine M. De Nardo
Author: Mamadou Daffé
Author: Geanncarlo Lugo-Villarino
Author: Prashant Kesharwani
Author: Kenneth Murphy
Author: Gerd Pluschke
Author: Mehmet Turgut
Author: Pere-Joan Cardona