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Author: Esther Nobs Publisher: ISBN: 9789180399524 Category : Languages : en Pages : 0
Book Description
Infection represents a complex interplay between invading microorganisms and the immune system. The immune system dynamically responds to the presence of pathogens, employing various defence mechanisms to neutralize and eliminate invaders. However, pathogens have evolved strategies to evade detection and elimination, leading to infections. This thesis focuses on mycobacterial regulation of macrophages, a key interplay in the pathogenesis of tuberculosis. The macrophage aims to neutralize intruding mycobacteria through the process of phagocytosis, however, Mycobacterium tuberculosis evades the phagosome, allowing it to gain access to the cytosol of the macrophage. From here it manipulates macrophage functions and other immune responses. The specialized protein secretion system ESX-1 is required for full virulence of mycobacteria and is involved in evasion strategies such as phagosomal escape and induction of type I interferons. The role of type I interferons in mycobacterial infection remains incompletely understood, although evidence strongly suggests a host detrimental role. The work presented in this thesis brings light on these key events during mycobacterial infection and contributes with new insights regarding the onset and functional role of the type I interferon response during infection.
Author: Esther Nobs Publisher: ISBN: 9789180399524 Category : Languages : en Pages : 0
Book Description
Infection represents a complex interplay between invading microorganisms and the immune system. The immune system dynamically responds to the presence of pathogens, employing various defence mechanisms to neutralize and eliminate invaders. However, pathogens have evolved strategies to evade detection and elimination, leading to infections. This thesis focuses on mycobacterial regulation of macrophages, a key interplay in the pathogenesis of tuberculosis. The macrophage aims to neutralize intruding mycobacteria through the process of phagocytosis, however, Mycobacterium tuberculosis evades the phagosome, allowing it to gain access to the cytosol of the macrophage. From here it manipulates macrophage functions and other immune responses. The specialized protein secretion system ESX-1 is required for full virulence of mycobacteria and is involved in evasion strategies such as phagosomal escape and induction of type I interferons. The role of type I interferons in mycobacterial infection remains incompletely understood, although evidence strongly suggests a host detrimental role. The work presented in this thesis brings light on these key events during mycobacterial infection and contributes with new insights regarding the onset and functional role of the type I interferon response during infection.
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: 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: Suzie Hingley-Wilson Publisher: Frontiers Media SA ISBN: 2832519164 Category : Medical Languages : en Pages : 297
Book Description
The macrophage (or “big eater”) is often considered the first cell type to encounter the causative agent of Tuberculosis (TB), Mycobacterium tuberculosis, upon entry to the lung. Once inside the macrophage the tubercle bacillus can survive and even replicate where many other invading pathogens perish. Recent research suggests the bacilli adapts within this hostile environment, treating the macrophage like a Trojan horse. Indeed, cutting-edge techniques have revealed that the degree of bacterial heterogeneity and resistance to antibiotics changes within the macrophage. M. tuberculosis spends most of its life cycle within the macrophage and has adopted specific mechanisms to survive, egress and to recruit more of this niche cell (eg the Type VII secretion system ESX-1). Understanding the host-pathogen interaction in tuberculous infection is key to understanding TB, which remains the number one cause of death from a bacterial infection. In this research topic we aim to cover advances in understanding how the tubercle bacillus adapts and survives within the host cell. Determining the responsible mechanisms may reveal novel ways to target this deadly pathogen and halt its adaptation and transformation within these potentially destructive or permissive cells.
Author: Dorothee Heemskerk Publisher: Springer ISBN: 3319191322 Category : Medical Languages : en Pages : 71
Book Description
This work contains updated and clinically relevant information about tuberculosis. It is aimed at providing a succinct overview of history and disease epidemiology, clinical presentation and the most recent scientific developments in the field of tuberculosis research, with an emphasis on diagnosis and treatment. It may serve as a practical resource for students, clinicians and researchers who work in the field of infectious diseases.
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: Edward Thompson Richardson (III) Publisher: ISBN: Category : Immunology Languages : en Pages : 0
Book Description
Mycobacterium tuberculosis, the cause of tuberculosis, survives for long periods in a latent state in infected individuals, and the immune system is typically able to control but not eliminate the bacteria. Latency is a complex phenomenon but involves, in part, interactions of the bacteria and its unique lipoproteins and lipoglycans with macrophages, the main cells that become infected. The purpose of this dissertation was to expand understanding of how M. tuberculosis engages with macrophages. In the first part, we characterized the lipoglycan binding function of M. tuberculosis lipoprotein LprG. We determined the binding properties of these M. tuberculosis lipoglycans to LprG using surface plasmon resonance. We also verified the presence of a non-acyl chain dependent binding mode to LprG, and determined that LprG also binds mannan. Finally, we determined that one function of LprG is to facilitate exposure of LAM on the bacterial cell surface for interaction with macrophages. LprG-deficient M. tuberculosis had reduced surface-exposed lipoarabinomannan, and had reduced ability to block phagolysosome maturation, a known immune evasion mechanism that requires lipoarabinomannan. These studies contribute to understanding of LprG, and develop increased knowledge of how M. tuberculosis lipoarabinomannan is exposed to macrophages to block phagolysosome fusion, a process involved in bacterial persistence and intracellular survival. In the second part, we studied the TLR2 signaling response of macrophages to M. tuberculosis. We determined that TLR2 was required for M. tuberculosis to trigger NF-¿B and ERK, and that TLR2 signaling results in balanced downstream effects. NF-¿B is required for expression of pro-inflammatory IL-12, and M. tuberculosis-stimulated Tpl2-ERK signaling suppressed IL-12 while inducing anti-inflammatory IL-10. These effects reduced CD4+ T cell responses against M. tuberculosis. Tpl2-deficient macrophages expressed IL-12 in response to M. tuberculosis, and were more potent at stimulating antigen-specific T cells, upon initial stimulation and recall. These findings contribute to understanding of the signaling triggered by M. tuberculosis, and the role of the macrophage-intrinsic ERK cascade in inhibiting T cell-mediated host defense. Together, these studies expand understanding of the regulation of macrophages by M. tuberculosis in ways that promote long-term survival of the bacteria, and may potentiate latent infection.
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: Esther Nobs
Author: Esther Nobs
Author: Mark Verway
Author: Supriya Shukla
Author: Kenneth Murphy
Author: Jinhee Lee
Author: Suzie Hingley-Wilson
Author: Dorothee Heemskerk
Author: Christine M. De Nardo
Author: Edward Thompson Richardson (III)
Author: Gerd Pluschke