Download or read book Mycobacterial Regulation of Macrophage Responses to Infection written by Esther Nobs and published by . This book was released on 2024 with total page 0 pages. Available in PDF, EPUB and Kindle. Book excerpt: 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.
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 Modulation of Macrophage Signaling Pathways during Bacterial Infections written by Supriya Shukla and published by Frontiers Media SA. This book was released on 2021-08-18 with total page 259 pages. Available in PDF, EPUB and Kindle. Book excerpt:
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 Regulation of Immune Responses to Mycobacterial Infection written by Jinhee Lee and published by . This book was released on 2003 with total page 510 pages. Available in PDF, EPUB and Kindle. Book excerpt:
Download or read book Mycobacteria and the Macrophage written by Suzie Hingley-Wilson and published by Frontiers Media SA. This book was released on 2023-12-28 with total page 297 pages. Available in PDF, EPUB and Kindle. Book excerpt: 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.
Download or read book Tuberculosis in Adults and Children written by Dorothee Heemskerk and published by Springer. This book was released on 2015-07-17 with total page 71 pages. Available in PDF, EPUB and Kindle. Book excerpt: 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.
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 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 Regulation of Macrophages by Mycobacterium Tuberculosis and the ERK MAP Kinase Signaling Pathway written by Edward Thompson Richardson (III) and published by . This book was released on 2015 with total page 0 pages. Available in PDF, EPUB and Kindle. Book excerpt: 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.
Download or read book Mechanisms of Inhibition of Macrophage Responses to Interferon Gamma by Mycobacterium written by Eleanor Zoe Kincaid and published by . This book was released on 2005 with total page 434 pages. Available in PDF, EPUB and Kindle. Book excerpt:
Download or read book Immunology of Infectious Diseases written by Stefan H. E. Kaufmann and published by . This book was released on 2002 with total page 532 pages. Available in PDF, EPUB and Kindle. Book excerpt: Resumen: Offers an integrated view of principal aspects of immune response to all types of infectious agents. Deals with the immune system primarily as a host defense system. Various infectious agents and diseases are integrated under general topics rather than treated in separate chapters.
Download or read book Phagocytosis The Host written by S. Gordon and published by Elsevier. This book was released on 1999-11-22 with total page 543 pages. Available in PDF, EPUB and Kindle. Book excerpt: An accompanying volume (Volume 6) in this series presents strategies of cellular invasion from the viewpoint of the microbe.This filed of study is growing rapidly after a somewhat slow start over recent decades. This collection of invited chapters attempts to reflect current research, and brings together cell biologists, microbiologists and immunologists with disparate interests. However, there is a certain unity, even repetition of key themes, hopefully like a symphony rather than a boring catalogue. It will be evident that editorial bias favors intracellular paratism and medically important organisms. The neutrophil is far more than a supporting player to the macrophage, and some attempt is made to remind the reader of some of its unique skills. To retain a manageable size, the emphasis is on relatively early events such as mutual recognition, cell entry, and response, rather than on longterm changes in gene expression by either host cell or pathogen. Viruses are excluded not because of lack of importance but because of somewhat different research approaches, although it is cytogenes, share common strategies in invasion and intercellular spread.
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 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:
Download or read book The Roles of Innate like T Cells and Macrophages During Mycobacterium Marinum Infection in Xenopus Laevis written by Kun Hyoe (Jules) Park and published by . This book was released on 2019 with total page 121 pages. Available in PDF, EPUB and Kindle. Book excerpt: Mycobacterium marinum (Mm) infects many vertebrates including aquatic species and humans, causing persistent infections that are problematic for aquaculture and public health. Also, Mm serves as a BSL2 alternative pathogen for Mycobacterium tuberculosis (Mtb), the causative agent for human tuberculosis (TB). Innate-like T (iT) cells are restricted by non-polymorphic MHC class I-like molecules presenting conserved ligands and can regulate anti-mycobacterial immune responses. Thus, harnessing iT cells for novel immunotherapy is increasing attention to improve TB vaccines. As a part of the thesis work, we developed a comparative model in Xenopus laevis to study host-Mm responses of two life stages, adult and tadpole. Adults possess conventional T cell-mediated immunity, whereas tadpoles predominantly rely on iT cells. We hypothesized that tadpoles mount weaker anti-Mm immune responses and are more susceptible to Mm infection than adults. Our data refuted this hypothesis revealing that tadpoles are as resistant as adults to Mm infection. However, we unveiled distinct T cell-mediated responses against Mm between adults and tadpoles. Mm infection triggered a robust pro-inflammatory CD8 T cell response in adults, but a non-inflammatory CD4-like/iT cell-mediated response in tadpoles. Furthermore, adult anti-Mm responses produced granulomas surrounded by T cells and significantly reduced Mm loads, whereas tadpoles rarely exhibited granulomas and tolerated persistent Mm accumulation. Our group previously identified an anti-Mm iT cell subset (iV?45), which interacts with the cognate MHC class-I like, XNC4 molecule, is critical for tadpole's resistance to Mm infection. In my work, the complex interaction of iV?45 and other putative iT cell populations with XNC4 was further investigated using a MHC tetramer technology. I found that XNC4-tetramers+ T cells were recruited in the peritoneum and the liver in response to Mm dissemination in tadpoles. Preliminary TCR repertoire characterization of XNC4-tetramers+ T cells indicated limited TCR? rearrangement diversity in germinal configurations, suggesting that XNC4 interacts with a few iT cell subsets. Interestingly, a subset of Mm infected macrophages express the XNC4 on the surface, which led us postulate that Mm infected macrophages can directly interact with the iT cells via XNC4. Also, the Mm infected macrophages highly expressed IL-34 and iNOS, which are critical for M1-like macrophage effector functions in X. laevis. Therefore, our data suggest that the iV?45 T cells may recognize Mm infected macrophages and further regulate anti-mycobacterial effector functions of the macrophages. Together, the present work provides novel insights into the critical roles of MHC-like restricted iT cells in shaping macrophage-mediated host-mycobacteria interactions in vertebrates. In addition, our study can ultimately form foundations for developing new vaccine options targeting iT cells with conserved ligands for emerging mycobacterial infections including Mtb.
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.
