Immunology and Infectious Disease Commons^™

The Effects Of Diet And The Microbiome On Reproduction And Longevity: A Comparative Review Across 5 Continents, Stephanie N. Chilton, Megan K. Enos, Jeremy P. Burton, Gregor Reid

Microbiology & Immunology Publications

Human longevity and quality of life remain key societal drivers, but the healthcare burden of diet-related chronic diseases is economically unmanageable. In recent years, it has been proposed that the composition and abundance profiles of certain bacterial phyla in the gut are indicators of malnutrition, and ill health. But, how much does the gut microbiome and diet really contribute to outcomes? The description of three microbial enterotypes remains to be verified, as does its significance for health tested across continents and within people who migrate from one lifestyle to another. It is not simply that the diet of one region …

How Probiotics And The Microbiome Will Change Medical Practice, Gregor Reid

Microbiology & Immunology Publications

No abstract provided.

Characterization Of The Innate Response To The Ragb Protein Of Porphyromonas Gingivalis., Justin Hutcherson

Electronic Theses and Dissertations

More than 64 million people in the US suffer from some form of periodontal disease. Periodontal diseases are bacterial infections of the hard and soft tissues surrounding the teeth which can lead to tooth loss. Periodontal tissue destruction is caused by inflammatory host-pathogen interactions. Porphyromonas gingivalis is a major causative agent of periodontal diseases and is a keystone periodontal pathogen. The 55kDa immunodominant RagB outer membrane protein of P. gingivalis has been proposed to facilitate iron transport. However, potential interactions between RagB and the innate response have not been examined. RagB homologues in gut Bacteroidetes have been associated with inflammatory …

The Effect Of Activation Induced Cytidine Deaminase Phosphorylation And Herpes Virus Uracil Dna Glycosylase On Antibody Diversification, Marc Macaluso

Dissertations and Theses (Open Access)

Activation-induced cytidine deaminase (AID) is a mutagenic enzyme that is expressed in mammalian B-cells and initiates the antibody diversification processes of somatic hypermuntation (SHM) and isotype class switch recombination (CSR). AID is targeted to the immunoglobulin gene locus where it deaminates cytosines to generate uracil residues in DNA. This generates guanine-uracil (U:G) mismatch lesion which are recognized by uracil DNA glycosylase (UNG), a DNA repair enzyme that removes uracil from DNA and triggers downstream repair of the lesion. While UNG is a ubiquitously expressed DNA repair enzyme, its recognition and removal of AID introduced uracils is essential in both SHM …

Critical Insights Into The Pathogenesis Of Clinical Isolates Of Pandemic Influenza A(H1n1) 2009 Virus In Mouse And Ferret Models., Jeremy V. Camp 1980-

Electronic Theses and Dissertations

Influenza A virus (IAV) is a minus-sense, segmented, single-stranded RNA virus that infects the respiratory tract of humans and can cause severe illness. Novel IAV variants perpetually emerge on every continent, and the emergence of variants with increased transmissibility and/or pathogenesis in the human population is a serious concern for global public health. Infection with IAV typically causes an acute, self-limiting upper respiratory tract disease. However, severe IAV disease is characterized by infection of the lower respiratory tract which can lead to pneumonia and may result in the development of acute respiratory distress syndrome (ARDS). Viral and host contributions to …

Early Host Response And Immune Signaling To 2009 Pandemic Influenza A (H1n1) Viruses In Primary Cell Culture Models., Rachael Lask Gerlach

Electronic Theses and Dissertations

Influenza A virus (IAV) subtypes and even genotypes within subtypes can show differences in tropism (host, cell type), magnitude of infection, immune response and progression of illness. My dissertation focused on the development and use of two in vitro physiologically-relevant human cell culture models, well-differentiated normal human bronchial epithelial (wdNHBE) cells and human monocyte-derived macrophages (MDM) for the study of early IAV-host interactions. These models have given new insight into early host responses to seasonal H1N1 (BN59) and two pandemic A(H1N1)2009 viruses or H1N1pdm herein. The H1N1pdm are clinical isolates from a fatal (A/KY/180/10) and nonfatal (A/KY/136/09) case. In the …

Characterization And Investigation Of Fungi Inhabiting The Gastrointestinal Tract Of Healthy And Diseased Humans, Mallory J. Suhr

Department of Food Science and Technology: Dissertations, Theses, and Student Research

Gastrointestinal microbiome studies have failed to include fungi in total community analyses. As a result, their diversity and function in the gut is poorly understood. Recent work has begun to uncover the role intestinal fungi play in diet, immune system development, interactions with other microorganisms in the gut, and pathogenesis of diseases. Advances in sequencing technologies allow for the ability to profile the fungal gut microbiome (“mycobiome”) in healthy and diseased states. This thesis explores the mycobiome in 1) healthy humans with a vegetarian diet and 2) pediatric small bowel transplant recipients that develop fungal bloodstream infections.

The gut mycobiome …

Viral Bimolecular Fluorescence Complementation: A Novel Tool To Study Intracellular Vesicular Trafficking Pathways, Brennan S Dirk, Rajesh Abraham Jacob, Aaron L Johnson, Emily N Pawlak, P Craig Cavanagh, Logan Van Nynatten, S M Mansour Haeryfar, Jimmy D. Dikeakos

Microbiology & Immunology Publications

The Human Immunodeficiency Virus type 1 (HIV-1) accessory protein Nef interacts with a multitude of cellular proteins, manipulating the host membrane trafficking machinery to evade immune surveillance. Nef interactions have been analyzed using various in vitro assays, co-immunoprecipitation studies, and more recently mass spectrometry. However, these methods do not evaluate Nef interactions in the context of viral infection nor do they define the sub-cellular location of these interactions. In this report, we describe a novel bimolecular fluorescence complementation (BiFC) lentiviral expression tool, termed viral BiFC, to study Nef interactions with host cellular proteins in the context of viral infection. Using …

Genome-Wide Comparison Of Pu.1 And Spi-B Binding Sites In A Mouse B Lymphoma Cell Line, Lauren A. Solomon, Stephen K. H. Li, Jan Piskorz, Li S. Xu, Rodney P. Dekoter

Microbiology & Immunology Publications

Background

Spi-B and PU.1 are highly related members of the E26-transformation-specific (ETS) family of transcription factors that have similar, but not identical, roles in B cell development. PU.1 and Spi-B are both expressed in B cells, and have been demonstrated to redundantly activate transcription of genes required for B cell differentiation and function. It was hypothesized that Spi-B and PU.1 occupy a similar set of regions within the genome of a B lymphoma cell line.

Results

To compare binding regions of Spi-B and PU.1, murine WEHI-279 lymphoma cells were infected with retroviral vectors encoding 3XFLAG-tagged PU.1 or Spi-B. Anti-FLAG chromatin …

Inclusion Of Fermented Foods In Food Guides Around The World, Stephanie N. Chilton, Jeremy P. Burton, Gregor Reid

Microbiology & Immunology Publications

Fermented foods have been a well-established part of the human diet for thousands of years, without much of an appreciation for, or an understanding of, their underlying microbial functionality, until recently. The use of many organisms derived from these foods, and their applications in probiotics, have further illustrated their impact on gastrointestinal wellbeing and diseases affecting other sites in the body. However, despite the many benefits of fermented foods, their recommended consumption has not been widely translated to global inclusion in food guides. Here, we present the case for such inclusion, and challenge health authorities around the world to consider …

Immunotherapy For Human Breast Cancer, Nasrah Ali Al Kamal

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Al Kamal, Nasrah. M.S. Program of Microbiology and Immunology, Wright State University, 2015.Immunotherapy for Human Breast Cancer. The study focuses on the methodologies that are used in breast cancer therapy. The review finds major evolutions of these methods and the influence they have made on the increased survival rates in cancer patients. There is also a projection of the processes that are involved in the therapy practices and the way the protocols have been improved over time. The various stages of cancer treatment project the various aspects of better performance articulations in the therapy sector. There is also reference to …

Application Of Fluorescence In Situ Hybridization For Visualization And Quantification Of Human Gastrointestinal Microbiota, Alexander M. Gordon

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The microbiota of the human gastrointestinal tract is the focus of current research due to their role in human health and disease. Modern methods characterize the communities of gut microbiota through the use of culture independent techniques. Technologies such as microarrays and next generation sequencing (NGS) determine microbial profiles by analyzing the pool of 16S ribosomal small subunit RNA genes in the community. These techniques operate through the measurement of genomic content rather than through direct analysis of cells. This approach predisposes the methods to discrepancies and bias. In contrast, the use of fluorescence in situ hybridization (FISH) to analyze …

Francisella Tularensis Catalase Restricts Immune Function By Impairing Trpm2 Channel Activity, Nicole Lynn Flaherty

Legacy Theses & Dissertations (2009 - 2024)

As an innate defense mechanism, macrophages produce reactive species that weaken pathogens and serve as secondary messengers to modify signaling responses involved in immune function. The gram-negative bacterium F. tularensis utilizes its antioxidant armature to limit the host immune response but the mechanism behind this suppression has not been defined. Here we establish that F. tularensis limits Ca2+ entry thereby limiting actin reorganization and IL-6 production in a redox-dependent fashion. Wild-type (LVS) or catalase deficient F. tularensis (∆katG) show distinct profiles in their H2O2 scavenging capacity, 1 pM/sec and 0.015 pM/sec, respectively. Murine alveolar macrophages infected with ∆katG display distinct …

Determining The Role Of The Ahr In Immunoglobulin Expression And Class Switch Recombination, Bassam Fawaz Kashgari

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The aryl hydrocarbon receptor (AhR) is a ligand-activated cytosolic transcription factor that regulates xenobiotic-metabolizing enzymes. It mediates the toxicity of various environmental chemicals such as 2,3,7,8-tetracholorodibenzo-p-dioxin (TCDD). TCDD inhibits the differentiation of B cells into antibody-secreting cells and inhibits immunoglobulin (Ig) expression in various animal models. We have previously determined that TCDD-induced inhibition of the mouse Ig heavy chain gene (mo-Igh) is AhR-dependent. This inhibition may be mediated by binding of the AhR to dioxin response elements (DREs) within the 3'Igh regulatory region (3'IghRR) and inhibition of 3'IghRR activity, a significant transcriptional regulator of Ig expression. However, there are structural …

Role Of Crebh In Endotoxin Mediated Modulation Of Hepatic Metabolism, Aditya Prakash Dandekar

Wayne State University Dissertations

Bacterial endotoxins can induce a variety of physiological changes in the host. This effect is not only restricted to inflammatory changes but also comprises metabolic changes in the host body. Lipopolysaccharide (LPS), one of the key components of the bacterial cell walls, is capable of triggering host metabolic changes. Hyperlipidemia usually accompanies with high endotoxin levels as well as inflammation. Lipid metabolism disorders are one of the common hallmarks of a patient with sepsis or high levels of endotoxin through diet. Previously, we have identified an endoplasmic reticulum (ER) anchored liver-specific transcription factor CREBH (cAMP-responsive element-binding protein, hepatocyte-specific), which is …

Silver Nanoparticles Inhibit The Binding And Replication Of Dengue Virus, Kelley J. Williams

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Dengue is an emerging hemorrhagic fever virus and widely considered the most important arbovirus in the world. The CDC and the World Health Organization estimates Dengue virus (DENV) infects 50-400 million people annually in the tropical and subtropical regions of the world. More than 500 thousand of these will develop severe infection and approximately 22 thousand will lead to death. Dengue virus (DENV) is a positive-sense RNA virus that exists in 4 antigenic serotypes. An immunological phenomenon called antibody-dependent enhancement (ADE) leaves a DENV victim vulnerable to increased risk of subsequent infections. Secondary infections with DENV are known to increase …

The Impact Of Hsv-1 Infection On Cell Viability, Morphology, And Cd Markers Expression By Unpolarized And Cytokine-Polarized J774a.1 Mouse Macrophages, Sarah Saad Alsharif

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Macrophages play an important role in the immune system, particularly in neutralizing pathogens via phagocytosis and the production of multiple cytokines and chemokines that control infection after exposure to specific stimuli. Macrophages exhibit two different phenotypes, M1 and M2. This study evaluated the role of Suppressors of cytokine signaling (SOCS)1 and SOCS3 on Herpes Simplex Virus (HSV-1) infection of polarized macrophages, cell viability, cell morphology, and the expression of cell surface CD markers. I hypothesized that J774A.1 murine macrophages cells in the naive state (M0), and M1 and M2 phenotypes would display differences in CD markers CD80,CD163, and CD200R, cell …

Inhibition Of Nectin-1 And Herpes Virus Entry Mediator (Hvem) Using Monoclonal Antibodies Decreases Hsv-1 Entry Into Neuro-2a Cells, Erica Marie Rinehart

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This study examines the effects of blocking the nectin-1 and Herpes Virus Entry Mediator (HVEM) receptors on Neuro-2a (N2a) cells in order to prevent HSV-1 infection. These two receptors have been identified as a primary and secondary mode of entry for HSV-1. Since there was some debate about the correct serum level to be used in growth media for healthy N2a cells, three concentrations (2%, 5%, 10%) were used to examine relative growth and neurite development, in addition to examining possible differences in infectivity levels in all other experiments. There was a difference in general morphology, with neurite abundance and …

The Use Of Antibody-Coated Latex Beads To Determine Single Positive And Double Positive Mouse Spleen Cells Expressing Cd5 And/Or Cd19 Glycoproteins, Abdulrazzag Abdulaziz Othman

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Flow cytometry is the standard method used to diagnose, stage, and monitor patients' response to the treatment given by counting the numbers of CD5, CD19 and CD5+ CD19+ B lymphocytes. In this study, a comparison was done between numbers of single CD5+, single CD19+ and dual CD5+ CD19+ mouse spleen B lymphocytes using flow cytometry and antibody-latex beads. The bead method involved antibody-coated latex bead and yielded results similar to those of flow cytometry. For cells exhibiting both markers (CD5+ CD19+), the bead method used antibody-coated beads of two different colors yielded similar results to those of flow cytometry results. …

The Effect Of O Antigen Loss On The Protein Composition And Inflammatory Response Elicited By Klebsiella Pneumoniae, Bethaney Cahill

UNF Graduate Theses and Dissertations

Klebsiella pneumoniae is a Gram-negative pathogen associated with numerous infections. Like all Gram-negative bacteria, K. pneumoniae naturally release outer membrane vesicles (OMVs) during all stages of cellular growth. OMVs are composed of the outer membrane components such as lipopolysaccharide (LPS) and outer membrane proteins and contain cytosolic and periplasmic proteins in the lumen. K. pneumoniae is often found to lack an O antigen. The absence of the O antigen has been reported to alter the protein content of the membrane which may further alter the immune response elicited by K. pneumoniae. Therefore the purpose of this study was to …

Role Of Type Iv Pili In Predation By Bdellovibrio Bacteriovorus, Ryan M Chanyi, Susan F Koval

Microbiology & Immunology Publications

Bdellovibrio bacteriovorus, as an obligate predator of Gram-negative bacteria, requires contact with the surface of a prey cell in order to initiate the life cycle. After attachment, the predator penetrates the prey cell outer membrane and enters the periplasmic space. Attack phase cells of B. bacteriovorus have polar Type IV pili that are required for predation. In other bacteria, these pili have the ability to extend and retract via the PilT protein. B. bacteriovorus has two pilT genes, pilT1 and pilT2, that have been implicated in the invasion process. Markerless in-frame deletion mutants were constructed in a prey-independent mutant to …

Enhanced Expression Of Codon Optimized Mycobacterium Avium Subsp. Paratuberculosis Antigens In Lactobacillus Salivarius, Christopher D. Johnston, John P. Bannatine, Rodney Govender, Lorraine Endersen, Daniel Pletzer, Helge Weingart, Aidan Coffey, Jim O'Mahony, Roy D. Sleator

Department of Biological Sciences Publications

It is well documented that open reading frames containing high GC content show poor expression in A+T rich hosts. Specifically, G+C-rich codon usage is a limiting factor in heterologous expression of Mycobacterium avium subsp. paratuberculosis (MAP) proteins using Lactobacillus salivarius. However, re-engineering opening reading frames through synonymous substitutions can offset codon bias and greatly enhance MAP protein production in this host. In this report, we demonstrate that codon-usage manipulation of MAP2121c can enhance the heterologous expression of the major membrane protein (MMP), analogous to the form in which it is produced natively by MAP bacilli. When heterologously over-expressed, antigenic determinants …

Antiviral Responses In Mouse Embryonic Stem Cells: Differential Development Of Cellular Mechanisms In Type I Interferon Production And Response, Ruoxing Wang

Dissertations

Embryonic stem cells (ESCs) have been recognized as a promising cell source for regenerative medicine. Intensive research over the past decade has led to the possibility that ESC-derived cells will be used for the treatment of human diseases. However, increasing evidence indicates that ESC-derived cells generated by the current differentiation methods are not fully functional. It is recently recognized that ESC-derived cells lack innate immunity to a wide range of infectious agents and inflammatory cytokines. When used in patients, ESC-derived cells would be placed in wounded sites that are exposed to various pathogens and inflammatory cytokines; therefore, their viability and …

Potential Roles Of Peroxidases In Caenorhabditis Elegans Innate Immunity, George R. Tiller, George R. Tiller

Dissertations and Theses (Open Access)

The production of ROS (reactive oxygen species) in response to pathogen detection is a rapid, nonspecific response that is evolutionarily conserved from nematodes to humans. ROS serve as direct and indirect effectors of innate and adaptive immunity. In Caenorhabditis elegans, a ROS burst is observed during infection and is mediated by the dual oxidase BLI-3, which produces H₂O₂. RNAi (RNA interference) to reduce the amount of BLI-3 results in a significant increase in susceptibility to pathogens, suggesting BLI-3 has a role in the immune response. However, H₂O₂ by itself is not a …

Oroya Fever And Verruga Peruana: Bartonelloses Unique To South America, Michael F. Minnick, Burt E. Anderson, Amorce Lima, James M. Battisti, Phillip G. Lawyer, Richard J. Birtles

Biological Sciences Faculty Publications

Bartonella bacilliformis is the bacterial agent of Carrión's disease and is presumed to be transmitted between humans by phlebotomine sand flies. Carrión's disease is endemic to high-altitude valleys of the South American Andes, and the first reported outbreak (1871) resulted in over 4,000 casualties. Since then, numerous outbreaks have been documented in endemic regions, and over the last two decades, outbreaks have occurred at atypical elevations, strongly suggesting that the area of endemicity is expanding. Approximately 1.7 million South Americans are estimated to be at risk in an area covering roughly 145,000 km2 of Ecuador, Colombia, and Peru. Although disease …

Effect Of Chemotherapy On The Microbiota And Metabolome Of Human Milk: A Case Report, Camilla Urbaniak, Amy Mcmillan, Michelle Angelini, Gregory B Gloor, Mark Sumarah, Jeremy P Burton, Gregor Reid

Microbiology & Immunology Publications

BACKGROUND: Human milk is an important source of bacteria for the developing infant and has been shown to influence the bacterial composition of the neonatal gut, which in turn can affect disease risk later in life. Human milk is also an important source of nutrients, influencing bacterial composition but also directly affecting the host. While recent studies have emphasized the adverse effects of antibiotic therapy on the infant microbiota, the effects of maternal chemotherapy have not been previously studied. Here we report the effects of drug administration on the microbiota and metabolome of human milk.

METHODS: Mature milk was collected …

Understanding The Factors Affecting Microbiological Quality Of Wheat Milled Products: From Wheat Fields To Milling Operations, Luis E. Sabillón Galeas

Department of Food Science and Technology: Dissertations, Theses, and Student Research

Although regarded as a low-risk commodity, wheat flour-based mixes have been implicated in several food safety incidents. The present thesis is a compilation of five scientific manuscripts on the effect of weather variation, milling steps and implementation of pre-milling interventions on the microbiological quality and safety of wheat and milled products. The first manuscript is a review of the microbiological quality and safety of wheat-based products. Despite the low water activity, wheat flour may harbor dormant but viable microorganisms, which could lead to safety concerns when flour is used to produce refrigerated dough products. The second manuscript illustrates the effect …

Fty720 (Fingolimod) Provides Insight Into The Molecular Mechanisms Of Multiple Sclerosis, Madelyn Elizabeth Crawford

Pursuit - The Journal of Undergraduate Research at The University of Tennessee

Multiple sclerosis (MS) is a neurodegenerative disorder caused by a prolonged immune- mediated inflammatory response that targets myelin. Nearly all of the drugs approved for the treatment of MS are general immunosuppressants or only function in symptom management. The oral medication fingolimod, however, is reported to have direct therapeutic effects on cells of the central nervous system in addition to immunomodulatory functions. Fingolimod is known to interact with sphingosine-1-phosphate (S1P) receptors, and the most widely- accepted theory for its mechanism of action is functional antagonism of the receptor. This review examines significant neuromodulatory effects achieved by functional antagonism of the …

Use Of Cholera Toxin B As A Vaccine Adjuvant Activates Antigen Presenting Cells And Stimulates Production Of Pro-Inflammatory Cytokines, Heather C. Romlein

Seton Hall University Dissertations and Theses (ETDs)

Francisella tularensis is an intracellular pathogen that has been classified as a category “A” bioterrorism agent by the Centers For Disease Control. To date, there is no approved vaccine to provide protection against this pathogen. Previous in vivo studies with mice have shown that a mucosally targeted vaccine preparation of inactivated F. tularensis (iFt) adjuvanted with Cholera toxin “B” (CTB), successfully granted full protection against a less virulent strain (FT LVS) of the bacterium and provided partial protection against a more virulent strain (SchuS4). However, the mechanisms of this protection are not fully understood. In this …

Investigating Antibiotic Resistance Levels Of Salmonella Internalized In Lettuce Leaves, Jason B. Thomas

McNair Scholars Research Journal

Contamination of food crops by the human pathogen Salmonella is a food safety threat worldwide. Though using treated wastewater for irrigation is a sustainable practice, it may introduce trace levels of Salmonella that may contaminate food crops. Salmonella could develop resistance to antibiotics present in wastewater. The overall goal of the project is to increase the understanding of the public health risk associated with the use of treated wastewater to irrigate food crops. The objective of this particular study is to determine the antibiotic resistance level of Salmonella internalized in lettuce leaves. In this experiment, thirty-six plants of the lettuce …