Immunity Commons^™

Novel And Predominant Pathogen Responsible For The Enterovirus-Associated Encephalitis In Eastern China, Lei Zhang, Jie Yan, David M. Ojcius, Huakun Lv, Ziping Miao, Yin Chen, Yanjun Zhang, Jvying Yan

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Enteroviruses (EV) have been increasingly identified as the causative agent for unknown etiological encephalitis in many parts of the world, but the long period surveillance for enterovirus-associated encephalitis (EAE) was not reported in China. From 2002-2012 in Zhejiang, Coxsackieviruses A9, B1, B2, B3, B4, B5; and echoviruses 3, 4, 6, 9, 14, 25, 30 were detected from the unknown etiological encephalitis cases, with coxsackievirus B4 been identified here for the first time. From 2002-2004 and 2010-2012, echovirus 30 was found to be the periodically predominant serotype for in the EAE. The molecular typing results showed that all the EV isolates …

Aspects Of The Innate Immune System In The Caribbean Octocoral Swiftia Exserta, Lorenzo P. Menzel

FIU Electronic Theses and Dissertations

The immune systems of cnidaria are important to study for two reasons: to gain a better understanding of the evolution of immune responses, and to provide a basis to partially redress the precipitous world-wide die-offs of reef corals, some of which have been attributed to diseases and stress. Many immune responses share ancient evolutionary origins and are common across many taxa.

Using Swiftia exserta, an azooxanthellate ahermatypic local octocoral, as a proxy model organism to study aspects of innate immunity in corals and cnidaria allows us to address both of the reasons listed above while not using endangered species. …

Membrane Vesicles Nucleate Mineralo-Organic Nanoparticles And Induce Carbonate Apatite Precipitation In Human Body Fluids, Cheng-Yeu Wu, Jan Martel, Wei-Yun Cheng, Chao-Chih He, David M. Ojcius, John Ding-E. Young

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Recent studies indicate that membrane vesicles (MVs) secreted by various cells are associated with human diseases, including arthritis, atherosclerosis, cancer, and chronic kidney disease. The possibility that MVs may induce the formation of mineralo-organic nanoparticles (NPs) and ectopic calcification has not been investigated so far. Here, we isolated MVs ranging in size between 20 and 400 nm from human serum and FBS using ultracentrifugation and sucrose gradient centrifugation. The MV preparations consisted of phospholipid-bound vesicles containing the serum proteins albumin, fetuin-A, and apolipoprotein A1; the mineralization-associated enzyme alkaline phosphatase; and the exosome proteins TNFR1 and CD63. Notably, we observed that …

Identification Of Leptospira Interrogans Phospholipase C As A Novel Virulence Factor Responsible For Intracellular Free Calcium Ion Elevation During Macrophage Death, Jing-Fang Zhao, Hong-Hu Chen, David M. Ojcius, Xin Zhao, Dexter Sun, Yu-Mei Ge, Lin-Li Zheng, Xu'ai Lin, Lan-Juan Li, Jie Yan

All Dugoni School of Dentistry Faculty Articles

Background: Leptospira-induced macrophage death has been confirmed to play a crucial role in pathogenesis of leptospirosis, a worldwide zoonotic infectious disease. Intracellular free Ca²⁺ concentration ([Ca²⁺]i) elevation induced by infection can cause cell death, but [Ca²⁺]i changes and high [Ca²⁺]i-induced death of macrophages due to infection of Leptospira have not been previously reported.

Methodology/Principal Findings: We first used a Ca²⁺-specific fluorescence probe to confirm that the infection of L. interrogans strain Lai triggered a significant increase of [Ca²⁺]i in mouse J774A.1 or human THP-1 macrophages. Laser confocal microscopic examination …

Stomatin-Like Protein 2 Deficiency In T Cells Is Associated With Altered Mitochondrial Respiration And Defective Cd4+ T Cell Responses., Darah A Christie, Panagiotis Mitsopoulos, Julianna Blagih, Stanley D Dunn, Julie St-Pierre, Russell G Jones, Grant M Hatch, Joaquín Madrenas

Stanley D Dunn

Stomatin-like protein 2 (SLP-2) is a mostly mitochondrial protein that regulates mitochondrial biogenesis and function and modulates T cell activation. To determine the mechanism of action of SLP-2, we generated T cell-specific SLP-2-deficient mice. These mice had normal numbers of thymocytes and T cells in the periphery. However, conventional SLP-2-deficient T cells had a posttranscriptional defect in IL-2 production in response to TCR ligation, and this translated into reduced CD4(+) T cell responses. SLP-2 deficiency was associated with impaired cardiolipin compartmentalization in mitochondrial membranes, decreased levels of the NADH dehydrogenase (ubiquinone) iron-sulfur protein 3, NADH dehydrogenase (ubiquinone) 1β subcomplex subunit …

Role Of Branched-Chain Amino Acid Transporters In Staphylococcus Aureus Virulence, Sameha Omer

Electronic Thesis and Dissertation Repository

Branched-chain amino acids (BCAAs) act as effector molecules that signal a global transcriptional regulator, CodY, to regulate virulence factors in nutrient depleted environments. Staphylococcus aureus contains three putative BCAA transporters (BrnQ1, BrnQ2, BrnQ3) whose role in BCAA uptake is unknown. We hypothesize that BrnQ transporters are involved in BCAA uptake and contribute to virulence in S. aureus by modulating CodY activity. Results from radioactive uptake assays indicate that BrnQ1 is the predominant BrnQ transporter of isoleucine, valine and leucine. Meanwhile, BrnQ2 is more specific for isoleucine. Furthermore, only the lack of BrnQ1 hinders growth of S. aureus in chemically-defined media …

P2x4 Assembles With P2x7 And Pannexin-1 In Gingival Epithelial Cells And Modulates Reactive Oxygen Species Production And Inflammasome Activation, Shu-Chen Hung, Chul Hee Choi, Najwane Said-Sadier, Larry Johnson, Kalina Rosenova Atanasova, Hanen Sellami, Özlem Yilmaz, David M. Ojcius

All Dugoni School of Dentistry Faculty Articles

We have previously reported that Porphyromonas gingivalis infection of gingival epithelial cells (GEC) requires an exogenous danger signal such as ATP to activate an inflammasome and caspase-1, thereby inducing secretion of interleukin (IL)-1β. Stimulation with extracellular ATP also stimulates production of reactive oxygen species (ROS) in GEC. However, the mechanism by which ROS is generated in response to ATP, and the role that different purinergic receptors may play in inflammasome activation, is still unclear. In this study, we revealed that the purinergic receptor P2X₄ is assembled with the receptor P2X₇ and its associated pore, pannexin-1. ATP induces ROS …

The Role Of Α5gaba(A) Receptors In Brain Inflammation, Jason K. Wong

Electronic Thesis and Dissertation Repository

Microglia critically regulate brain inflammation. GABA_A receptors that contain the α5-subunit (α5GABA_A) exhibit high sensitivity to GABA and confer tonic activity. Moreover, α5GABA­_A receptors have been associated with brain inflammation. This study investigates the role of α5GABA_A receptors in microglial activation. Immunohistochemistry revealed that in response to intraperitoneal lipopolysaccharide (LPS), α5-subunit null mice exhibited significantly higher expression of IL-1β in hippocampal microglia. Neuronal-glial co-cultures treated with α5GABA­_A receptor inverse agonist L655,708 drastically increased microglial IL-1β expression. Surprisingly, ELISA of media from L655,708-treated co-cultures revealed a considerably lower concentration of IL-1β. Treating cultured primary astrocytes …

Characterization Of The Gut Microbiota And Colitogenic Bacterial Species In Core 1 O-Glycans Deficient Mice, Maria E. Perez-Munoz

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

Mucus is one important component of the intestinal mucosal barrier, and loss of its functionality is associated with colitis in humans and mice. Mice deficient in core 1 O-glycans (TM-IEC C1galt1^-/-) display a thinner mucus layer upon mutation of the glycosyltransferase enzyme (C1GALT1) responsible for core 1 O-glycans attachment, thus constituting an experimental model for human Ulcerative Colitis (UC). Under conventional conditions, these mice experience spontaneous inflammation of the colon. However, the exact role of the microbiota in colitis development in these mice has not been systematically investigated.

Aimed to gain insights into the role of …

Human Adenovirus E1a Binds And Retasks Cellular Hbre1, Blocking Interferon Signalling And Activating Virus Early Gene Transcription, Gregory J. Fonseca

Electronic Thesis and Dissertation Repository

Upon infection, human adenovirus (HAdV) must block interferon signaling and activate the expression of its early genes to reprogram the cellular environment to support virus replication. During the initial phase of infection, these processes are orchestrated by the first HAdV gene expressed during infection, early region 1A (E1A). E1A binds and appropriates components of the cellular transcriptional machinery to modulate cellular gene transcription and activate viral early genes transcription. We have identified hBre1/RNF20 as a novel target of E1A. hBre1 is an E3 ubiquitin ligase which acts with the Ube2b E2 conjugase and accessory factors RNF40 and WAC1 to monoubiquitinate …

Inflammatory Breast Cancer: The Immune Perspective, Evan N. Cohen

Dissertations & Theses (Open Access)

Inflammatory breast cancer (IBC) is the most insidious form of locally advanced disease. Although rare and less than 2% of all breast cancer, IBC is responsible for up to 10% of all breast cancer deaths. Despite the name, very little is known about the role of inflammation or immune mediators in IBC. Therefore, we analyzed blood samples from IBC patients and non-IBC patients, as well as healthy donor controls to establish an IBC-specific profile of peripheral blood leukocyte phenotype and function of T cells and dendritic cells and serum inflammatory cytokines.

Emerging evidence suggests that host factors in the microenviromement …

Evolutionary And Molecular Analysis Of Conserved Vertebrate Immunity To Fungi, Erin Carter

Honors College

The innate immune system is highly conserved amongst all multicellular organisms. Yet a constant battle exists between host cells and pathogens due to the rapid evolution of immune system components. Functional genomics and in silico methods can be employed to elucidate the evolutionary patterns of vertebrate immunity to pathogenic fungi such as Candida albicans, an opportunistic fungal pathogen that can cause lethal candidiasis in the immunocompromised. Mammals such as humans and mice possess conserved C-type lectin receptors that recognize the C. albicans cell wall. However, these receptors have not been identified in fish. Here I describe how we identified potential …

Characterization Of Differentiation And Prognostic Biomarkers On Cd8+ Tumor-Infiltrating Lymphocytes In Metastatic Melanoma, Richard C. Wu

Dissertations & Theses (Open Access)

CD8⁺ cytotoxic T lymphocytes (CTL) frequently infiltrate tumors, yet most melanoma patients fail to undergo tumor regression. We studied the differentiation of the CD8⁺ tumor-infiltrating lymphocytes (TIL) from 44 metastatic melanoma patients using known T-cell differentiation markers. We also compared CD8⁺ TIL against the T cells from matched melanoma patients’ peripheral blood. We discovered a novel subset of CD8⁺ TIL co-expressing early-differentiation markers, CD27, CD28, and a late/senescent CTL differentiation marker, CD57. This CD8⁺CD57⁺ TIL expressed a cytolytic enzyme, granzyme B (GB), yet did not express another cytolytic pore-forming molecule, perforin (Perf). In …

Cellular Adaptation Of Macrophages To Anthrax Lethal Toxin-Induced Pyroptosis Via Epigenetic Mechanisms, Chae Young Han

Electronic Thesis and Dissertation Repository

Cellular adaptation to microbial stresses has been demonstrated in several cell types. Macrophages (MФ) are sentinel immune cells fending off invading microbes. Anthrax lethal toxin (LeTx) is a key virulence factor released by Bacillus anthracis that causes rapid cell death, pyroptosis. A small number of RAW246.7 macrophages (~4%) exposed to a non-lethal dose of LeTx become resistant to LeTx-induced pyroptosis for ~ 4 weeks, termed “toxin-induced resistance (TIR)”. Here, I showed that high levels of DNA methyl transferase1 (DNMT1) expression were maintained although global genomic methylation levels were not high in TIR. TIR cells treated with the DNMT inhibitor 5-azacitidine …

Hirsutella Sinensis Mycelium Suppresses Interleukin-1b And Interleukin-18 Secretion By Inhibiting Both Canonical And Non-Canonical Inflammasomes, Tsung-Teng Huang, Kowit-Yu Chong, David M. Ojcius, Yi-Hui Wu, Yun-Fei Ko, Cheng-Yeu Wu, Jan Martel, Chia-Chen Lu, Hsin-Chih Lai, John Ding-E. Young

All Dugoni School of Dentistry Faculty Articles

Cordyceps sinensis is a medicinal mushroom used for centuries in Asian countries as a health supplement and tonic. Hirsutella sinensis—the anamorphic, mycelial form of C. sinensis—possesses similar properties, and is increasingly used as a health supplement. Recently, C. sinensis extracts were shown to inhibit the production of the pro-inflammatory cytokine IL-1β in lipopolysaccharide-treated macrophages. However, the molecular mechanism underlying this process has remained unclear. In addition, whether H. sinensis mycelium (HSM) extracts also inhibit the production of IL-1β has not been investigated. In the present study, the HSM extract suppresses IL-1β and IL-18 secretion, and ATP-induced activation of caspase-1. Notably, …

Increased Toll-Like Receptor (Tlr) Mrna Expression In Monocytes Is A Feature Of Metabolic Syndrome In Adolescents, Olga Hardy, Albert Kim, Carol Ciccarelli, Laura Hayman, Jean Wiecha

Laura L. Hayman

BACKGROUND: Metabolic syndrome (MetSyn) is diagnosed frequently in some but not all overweight adolescents. Chronic inflammation, as seen in obesity, is strongly associated with MetSyn. OBJECTIVES: The aim of this pilot study was to assess the correlation between activation of the innate immune system and MetSyn, independent of body mass index (BMI), in a young population. METHODS: We quantitatively measured both systemic pro-inflammatory cytokines and gene expression of Toll-like receptors (TLRs) and downstream cytokines in circulating monocytes obtained from nine adolescents with metabolic syndrome (Overwt-MetSyn) and eight BMI-matched controls (Overwt-Healthy). RESULTS: The Overwt-MetSyn group demonstrated a significant elevation in expression …

On T Cell Fate Decisions: Retinol, Metabolism And Itreg Differentiation, Gavin I. Ellis

Theses and Dissertations--Microbiology, Immunology, and Molecular Genetics

The mammalian immune system is equipped to both eliminate pathogenic microorganisms and tumors, while remaining in homeostasis with commensal species at mucosal surfaces and tolerant towards self. Suppressor regulatory T cells (Tregs) are a major sentinel of this immunological tolerance. Induced Tregs (iTregs) arise in the periphery following the integration of cues from the metabolites, cytokines, etc. which make up its milieu. Dysregulation of iTreg development, function or homing underlies the etiology of many autoimmune diseases and immunopathologies. The amelioration or prevention of multiple murine disease models by boosting Treg cell numbers foreshadows clinical efficacy of iTreg therapy, but an …

Wallace H. Coulter: Decades Of Invention And Discovery, Joseph Robinson

Joseph P Robinson

Only a few inventors can be said to have made as great an impact on mankind as Wallace Coulter. His inquisitive mind and ability to see well beyond what existed served him well for 40 years of inventing. So many of the fundamental tools that exist today in the area of hematology were derived from or driven by Coulter's inventions that he could be called the most technological innovator in the field of modern hematology. In achieving these discoveries Wallace Coulter was clearly capable of visualizing future opportunities that few others recognized. His vision was combined with an uncanny ability …