Immunology and Infectious Disease Commons^™

Evidence For Using Immunosuppressive Treatments When Treating Idiopathic Non-Infectious Uveitis: A Systematic Review And Meta-Analysis, Hargurinder Singh

Electronic Thesis and Dissertation Repository

Idiopathic non-infectious uveitis is the spontaneous inflammation of the eye, which can lead to blindness if not treated correctly. Due to long-term side effects of corticosteroids, 4 classes of off-label immunosuppressive treatments are sometimes used (alkylating agents, inhibitors of T-lymphocyte signalling, antimetabolites and biological modifiers). We conducted a systematic review and meta-analysis to assess the effectiveness of different treatment classes on uveitis patients with similar characteristics. Results of the systematic review concurred with the conclusions from the meta-analysis, which found that all immunosuppressive treatments improved patient vision, with a statistically significant change in logMAR of -0.11 (95% CI of -0.152 …

A Novel Consortium Of Lactobacillus Rhamnosus And Streptococcus Thermophilus For Increased Access To Functional Fermented Foods, Remco Kort, Nieke Westerik, L. Mariela Serrano, François P. Douillard, Willi Gottstein, Ivan M. Mukisa, Coosje J. Tuijn, Lisa Basten, Bert Hafkamp, Wilco C. Meijer, Bas Teusink, Willem M. Vos, Gregor Reid, Wilbert Sybesma

Microbiology & Immunology Publications

Background: The lactic acid bacterium Lactobacillus rhamnosus GG is the most studied probiotic bacterium with proven health benefits upon oral intake, including the alleviation of diarrhea. The mission of the Yoba for Life foundation is to provide impoverished communities in Africa increased access to Lactobacillus rhamnosus GG under the name Lactobacillus rhamnosus yoba 2012, world's first generic probiotic strain. We have been able to overcome the strain's limitations to grow in food matrices like milk, by formulating a dried starter consortium with Streptococcus thermophilus that enables the propagation of both strains in milk and other food matrices. The affordable seed …

Meningeal Infiltration Of The Spinal Cord By Non-Classically Activated B Cells Is Associated With Chronic Disease Course In A Spontaneous B Cell-Dependent Model Of Cns Autoimmune Disease, Amy K. Dang, Yodit Tesfagiorgis, Rajiv W. Jain, Heather C. Craig, Steven M. Kerfoot

Microbiology & Immunology Publications

We characterized B cell infiltration of the spinal cord in a B cell-dependent spontaneous model of central nervous system (CNS) autoimmunity that develops in a proportion of mice with mutant T and B cell receptors specific for myelin oligodendrocyte glycoprotein. We found that, while males are more likely to develop disease, females are more likely to have a chronic rather than monophasic disease course. B cell infiltration of the spinal cord was investigated by histology and FACs. CD4⁺ T cell infiltration was pervasive throughout the white and in some cases gray matter. B cells were almost exclusively restricted to …

Local Bacteria Affect The Efficacy Of Chemotherapeutic Drugs, Panos Lehouritis, Joanne Cummins, Michael Stanton, Carola T Murphy, Florence O Mccarthy, Gregor Reid, Camilla Urbaniak, William L Byrne, Mark Tangney

Microbiology & Immunology Publications

In this study, the potential effects of bacteria on the efficacy of frequently used chemotherapies was examined. Bacteria and cancer cell lines were examined in vitro and in vivo for changes in the efficacy of cancer cell killing mediated by chemotherapeutic agents. Of 30 drugs examined in vitro, the efficacy of 10 was found to be significantly inhibited by certain bacteria, while the same bacteria improved the efficacy of six others. HPLC and mass spectrometry analyses of sample drugs (gemcitabine, fludarabine, cladribine, CB1954) demonstrated modification of drug chemical structure. The chemoresistance or increased cytotoxicity observed in vitro with sample drugs …

A Multi-Platform Metabolomics Approach Identifies Highly Specific Biomarkers Of Bacterial Diversity In The Vagina Of Pregnant And Non-Pregnant Women, Amy Mcmillan, Stephen Rulisa, Mark Sumarah, Jean M Macklaim, Justin Renaud, Jordan E Bisanz, Gregory B Gloor, Gregor Reid

Microbiology & Immunology Publications

Bacterial vaginosis (BV) increases transmission of HIV, enhances the risk of preterm labour, and is associated with malodour. Clinical diagnosis often relies on microscopy, which may not reflect the microbiota composition accurately. We use an untargeted metabolomics approach, whereby we normalize the weight of samples prior to analysis, to obtained precise measurements of metabolites in vaginal fluid. We identify biomarkers for BV with high sensitivity and specificity (AUC = 0.99) in a cohort of 131 pregnant and non-pregnant Rwandan women, and demonstrate that the vaginal metabolome is strongly associated with bacterial diversity. Metabolites associated with high diversity and clinical BV …

Characterization Of The Atsr/Atst Global Regulatory Pathway In Burkholderia Ceocepacia, Maryam Khodai-Kalaki

Electronic Thesis and Dissertation Repository

Phosphorylation cascades governed by two-component signal transduction systems provide key signalling mechanisms in bacteria, simple eukaryotes and higher plants, allowing them to translate signals into adaptive responses. These regulatory pathways consist of a transmembrane sensor protein that responds to an environmental cue leading to autophosphorylation, followed by the transfer of the phosphate to a cytoplasmic response regulator. Here, I study AtsR, a membrane-bound hybrid sensor kinase of Burkholderia cenocepacia, that negatively regulates quorum sensing related virulence factors such as biofilm, type 6-secretion and protease secretion. B. cenocepacia is a Gram-negative opportunistic pathogen which causes severe, chronic respiratory infections in …

Granulocyte Colony-Stimulating Factor: Its Role In Gut-Homing Macrophage Generation And Colitis, And Production By Probiotics, Shahab Meshkibaf

Electronic Thesis and Dissertation Repository

The pleiotropic cytokine granulocyte-colony stimulatory factor (G-CSF) is mainly required for the generation of neutrophils, but its role in macrophage generation has also been reported. In addition, G-CSF is effective for the down-regulation of inflammatory cytokines and ameliorating gut disorders, such as colitis. However, the G-CSF function in macrophage generation and gut immunity remains unclear. The first focus of this thesis was to assess the role of G-CSF in macrophage generation and its contribution to gut immunity. G-CSF was found to promote the generation of Gr-1high/F4/80+ macrophages in macrophage (M)-CSF-treated bone marrow cells, most likely through suppressing cell death. Gr-1high …

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.

The E26 Transformation-Specific Transcription Factors Pu.1, Spi-B, And Spi-C Regulate Transcriptional Activation And Repression Of Nfkb1 To Control B Cell Development And Function, Stephen Ka Ho Li

Electronic Thesis and Dissertation Repository

PU.1, Spi-B, and Spi-C are highly related E26 transformation-specific family transcription factors that can bind nearly identical DNA sequences. PU.1 and Spi-B (encoded by Spi1 and Spib respectively) are important for B cell development and function, but the function of Spi-C (encoded by Spic) in B cells is not clear. The objective of this study was to determine PU.1, Spi-B, and Spi-C’s function during B cell development, and during TLR-mediated responses. It was hypothesized that PU.1 and Spi-B were required for positively regulating components of TLR responses, and Spi-C inhibited PU.1 and Spi-B targets. Spi1^+/-Spib^-/- ( …

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 …

Ecological And Evolutionary Interactions Between Song Sparrows (Melospiza Melodia) And Their Bloodborne Parasites, Yanina Sarquis-Adamson

Electronic Thesis and Dissertation Repository

Local adaptation is the result of natural selection operating at a local scale, such that trade-offs in fitness across different environments result in individuals having higher fitness in their place of origin than when transported into a foreign environment. Populations may become locally adapted to features of their abiotic environment, or in the case of coevolutionary arms races between hosts and parasites, to other species comprising their biotic environment. If host populations are adapted to their local (sympatric) parasites, or conversely if parasites are adapted to their local hosts, then interactions with local parasite strains may influence the fitness consequences …

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 …