Medical Immunology Commons^™

Biliary Microbiota, Gallstone Disease And Infection With Opisthorchis Felineus., Irina V. Saltykova, Vjacheslav A Petrov, Maria D Logacheva, Polina G Ivanova, Nikolay V Merzlikin, Alexey E Sazonov, Ludmila M Ogorodova, Paul J. Brindley

Microbiology, Immunology, and Tropical Medicine Faculty Publications

BACKGROUND: There is increasing interest in the microbiome of the hepatobiliary system. This study investigated the influence of infection with the fish-borne liver fluke, Opisthorchis felineus on the biliary microbiome of residents of the Tomsk region of western Siberia.

METHODOLOGY/PRINCIPAL FINDINGS: Samples of bile were provided by 56 study participants, half of who were infected with O. felineus, and all of who were diagnosed with gallstone disease. The microbiota of the bile was investigated using high throughput, Illumina-based sequencing targeting the prokaryotic 16S rRNA gene. About 2,797, discrete phylotypes of prokaryotes were detected. At the level of phylum, bile from …

Dietary Nitrate Increases Exercise Tolerance In Patients With Non-Ischemic, Dilated Cardiomyopathy-A Double-Blind, Randomized, Placebo-Controlled, Crossover Trial., Conor Kerley, James O'Neill, Venu Reddy Bijjam, Ciara Blaine, Philip James, Liam Cormican

Articles

No abstract provided.

A Cell Cycle-Regulated Toxoplasma Deubiquitinase, Tgotud3a, Targets Polyubiquitins With Specific Lysine Linkages, Animesh Dhara, Anthony P. Sinai

Microbiology, Immunology, and Molecular Genetics Faculty Publications

The contribution of ubiquitin-mediated mechanisms in the regulation of the Toxoplasma gondii cell cycle has remained largely unexplored. Here, we describe the functional characterization of a T. gondii deubiquitinase (TGGT1_258780) of the ovarian-tumor domain-containing (OTU) family, which, based on its structural homology to the human OTUD3 clade, has been designated TgOTUD3A. The TgOTUD3A protein is expressed in a cell cycle-dependent manner mimicking its mRNA expression, indicating that it is regulated primarily at the transcriptional level. TgOTUD3A, which was found in the cytoplasm at low levels in G₁ parasites, increased in abundance with the progression of the …

Microrna Mir-155 Is Necessary For Efficient Gammaherpesvirus Reactivation From Latency, But Not For Establishment Of Latency, Rebecca L. Crepeau, Peisheng Zhang, Edward J. Usherwood

Dartmouth Scholarship

MicroRNA-155 (miR-155) has been shown to play significant roles in the immune response, including in the formation of germinal centers (GC) and the development and maturation of T follicular helper (Tfh) cells. There is in vitro evidence to support a critical role for cellular miR-155 and viral miR-155 homologs in the establishment of gammaherpesvirus latency in B cells. We sought to determine the contribution of miR-155 to the establishment and maintenance of latency in vivousing murine gammaherpesvirus (MHV-68) infection. MHV-68-infected mice deficient in miR-155 exhibited decreases in GC B cells and Tfh cells. However, the frequencies of spleen cells …

Brief Report: Hiv-1 Gp120 T-Cell Responses Correspond To Infection Outcomes In The Global Iprex Chemoprophylaxis Trial., Peter J Kuebler, Brian I Shaw, Kaitlyn S Leadabrand, Megha L Mehrotra, Robert M Grant, Esper G Kallás, Douglas F Nixon

Microbiology, Immunology, and Tropical Medicine Faculty Publications

Association of HIV-1-specific T-cell responses to infection risk in seronegative individuals is controversial. We quantified and phenotypically characterized gp120-specific T-cell responses in HIV-1 exposed, but uninfected subjects enrolled in the global Pre-exposure Prophylaxis Initiative (iPrEx) chemoprophylaxis trial. IFNγ ELISpot responses were detected in 24% of subjects irrespective of infection outcome. HIV-1 gp120 envelope-specific T-cell responses were more uniformly IFN-γ+TNF-α+Mip-1β+ in persistently seronegative subjects relative to subjects who later seroconverted (median frequency of 76.5% and 66.5%, respectively). IFNγ responses targeted the V2 loop for subjects who remained seronegative. HIV-1 gp120 envelope V2 loop-specific CD8 T-cell responses may help to protect against …

Proteomic Profiling Of Serum Derived Exosomes From Prostate Cancer Patients, David Turay

Loma Linda University Electronic Theses, Dissertations & Projects

Touted among the major achievements in the diagnosis and management of Prostate cancer (PCa) in the past few decades has been, the dramatic decline of men with advanced/metastatic PCa at diagnosis coupled with a significant improvement ( >90%) in the five and ten year survival rates of the disease. Non-palpable PCa (potentially clinically treatable disease) now accounts for 70-80% of all newly diagnosed cases of PCa. Preceding these changes by about a decade was the introduction of Prostatic Specific Antigen (PSA) into clinical practice; first as biomarker for monitoring response to therapy and subsequently as a complementary screening tool. It …

Mechanism Of Chimeric Vaccine Mediated Immune Suppression Of Human Dendritic Cells, Jacques Christian Mbongue

Loma Linda University Electronic Theses, Dissertations & Projects

Type 1 diabetes mellitus is a chronic inflammatory disease in which insulin producing β-cells of the pancreatic islets are killed by autoreactive cells of the immune system in response to a loss of tolerance. Dendritic cells (DC) interact predominantly with naïve T cells to regulate the delicate balance between immunity and tolerance required to maintain immunological homeostasis. In this dissertation, immature human dendritic cells (iDC) were inoculated with a chimeric fusion protein vaccine containing the pancreatic β-cell auto-antigen proinsulin linked to a mucosal adjuvant the cholera toxin B subunit (CTB-INS). Proteomic analysis of vaccine inoculated DCs revealed strong up-regulation of …

Needle In The Haystack: Combining Intravital Imaging And Mathematical Modeling To Understand How Vaccine-Induced T Cells Find Malaria-Infected Cells In Murine Livers, Vitaly V. Ganusov, Ian Cockburn, Reka Kelemen

Biology and Medicine Through Mathematics Conference

No abstract provided.

Hiv-1 Genetic Variation Resulting In The Development Of New Quasispecies Continues To Be Encountered In The Peripheral Blood Of Well-Suppressed Patients., Will Dampier, Michael R Nonnemacher, Joshua Mell, Joshua Earl, Garth D Ehrlich, Vanessa Pirrone, Benjamas Aiamkitsumrit, Wen Zhong, Katherine Kercher, Shendra Passic, Jean W Williams, Jeffrey M Jacobson, Brian Wigdahl

Kimmel Cancer Center Faculty Papers

As a result of antiretroviral therapeutic strategies, human immunodeficiency virus type 1 (HIV-1) infection has become a long-term clinically manageable chronic disease for many infected individuals. However, despite this progress in therapeutic control, including undetectable viral loads and CD4+ T-cell counts in the normal range, viral mutations continue to accumulate in the peripheral blood compartment over time, indicating either low level reactivation and/or replication. Using patients from the Drexel Medicine CNS AIDS Research and Eradication Study (CARES) Cohort, whom have been sampled longitudinally for more than 7 years, genetic change was modeled against to the dominant integrated proviral quasispecies with …

Diffuse Traumatic Brain Injury Induces Prolonged Immune Sysregulation And Potentiates Hyperalgesia Following A Peripheral Immune Challenge, Rachel K. Rowe, Gavin I. Ellis, Jordan L. Harrison, Adam D. Bachstetter, Gregory F. Corder, Linda J. Van Eldik, Bradley K. Taylor, Francesc Marti, Jonathan Lifshitz

Microbiology, Immunology, and Molecular Genetics Faculty Publications

Background: Nociceptive and neuropathic pain occurs as part of the disease process after traumatic brain injury (TBI) in humans. Central and peripheral inflammation, a major secondary injury process initiated by the traumatic brain injury event, has been implicated in the potentiation of peripheral nociceptive pain. We hypothesized that the inflammatory response to diffuse traumatic brain injury potentiates persistent pain through prolonged immune dysregulation.

Results: To test this, adult, male C57BL/6 mice were subjected to midline fluid percussion brain injury or to sham procedure. One cohort of mice was analyzed for inflammation-related cytokine levels in cortical biopsies and serum along an …

Signaling In Effector Lymphocytes: Insights Toward Safer Immunotherapy, Kamalakannan Rajasekaran, Matthew J. Riese, Sridhar Rao, Li Wang, Monica Thakar, Charles Sentman, Subramaniam Malarkannan

Dartmouth Scholarship

Receptors on T and NK cells systematically propagate highly complex signaling cascades that direct immune effector functions, leading to protective immunity. While extensive studies have delineated hundreds of signaling events that take place upon receptor engagement, the precise molecular mechanism that differentially regulates the induction or repression of a unique effector function is yet to be fully defined. Such knowledge can potentiate the tailoring of signal transductions and transform cancer immunotherapies. Targeted manipulations of signaling cascades can augment one effector function such as antitumor cytotoxicity while contain the overt generation of pro-inflammatory cytokines that contribute to treatment-related toxicity such as …

Genetic Predisposition And M1 Macrophage Polarization Created By Elastin-Derived Peptides Drive Abdominal Aortic Aneurysm Formation, Matthew A. Dale

Theses & Dissertations

Abdominal aortic aneurysm (AAA) is a dynamic vascular disease characterized by inflammatory cell invasion and extracellular matrix (ECM) degradation. Evidence has demonstrated a profound influence of genetic background on AAA formation. The work presented herein discusses two studies: the first demonstrates how genetic components can enhance the susceptibility to AAA formation and the second demonstrates how ECM degradation enhances AAA progression by influencing inflammatory cell phenotypes. An understanding of the pathways involved in AAA pathogenesis can help not only to identify potential patients at risk of AAA development, a heritable disease in which the incriminating component has yet to be …

Ifn-Γ Receptor And Stat1 Signaling In B Cells Are Central To Spontaneous Germinal Center Formation And Autoimmunity., Phillip P. Domeier, Sathi Babu Chodisetti, Chetna Soni, Stephanie L. Schell, Melinda J. Elias, Eric B. Wong, Timothy K. Cooper, Daisuke Kitamura, Ziaur S.M. Rahman

Department of Microbiology and Immunology Faculty Papers

Spontaneously developed germinal centers (GCs [Spt-GCs]) harbor autoreactive B cells that generate somatically mutated and class-switched pathogenic autoantibodies (auto-Abs) to promote autoimmunity. However, the mechanisms that regulate Spt-GC development are not clear. In this study, we report that B cell-intrinsic IFN-γ receptor (IFN-γR) and STAT1 signaling are required for Spt-GC and follicular T helper cell (Tfh cell) development. We further demonstrate that IFN-γR and STAT1 signaling control Spt-GC and Tfh cell formation by driving T-bet expression and IFN-γ production by B cells. Global or B cell-specific IFN-γR deficiency in autoimmune B6.Sle1b mice leads to significantly reduced Spt-GC and Tfh cell …

A Conserved Dna Repeat Promotes Selection Of A Diverse Repertoire Of Trypanosoma Brucei Surface Antigens From The Genomic Archive., Galadriel Hovel-Miner, Monica R. Mugnier, Benjamin Goldwater, George A. M. Cross, F. Nina Papavasiliou

Microbiology, Immunology, and Tropical Medicine Faculty Publications

African trypanosomes are mammalian pathogens that must regularly change their protein coat to survive in the host bloodstream. Chronic trypanosome infections are potentiated by their ability to access a deep genomic repertoire of Variant Surface Glycoprotein (VSG) genes and switch from the expression of one VSG to another. Switching VSG expression is largely based in DNA recombination events that result in chromosome translocations between an acceptor site, which houses the actively transcribed VSG, and a donor gene, drawn from an archive of more than 2,000 silent VSGs. One element implicated in these duplicative gene conversion events is a DNA repeat …

A Conserved Dna Repeat Promotes Selection Of A Diverse Repertoire Of Trypanosoma Brucei Surface Antigens From The Genomic Archive., Galadriel Hovel-Miner, Monica R Mugnier, Benjamin Goldwater, George A M Cross, F Nina Papavasiliou

Microbiology, Immunology, and Tropical Medicine Faculty Publications

African trypanosomes are mammalian pathogens that must regularly change their protein coat to survive in the host bloodstream. Chronic trypanosome infections are potentiated by their ability to access a deep genomic repertoire of Variant Surface Glycoprotein (VSG) genes and switch from the expression of one VSG to another. Switching VSG expression is largely based in DNA recombination events that result in chromosome translocations between an acceptor site, which houses the actively transcribed VSG, and a donor gene, drawn from an archive of more than 2,000 silent VSGs. One element implicated in these duplicative gene conversion events is a DNA repeat …

Impact Of Epigallocatechin-3-Gallate (Egcg), A Broad-Spectrum Anti-Inflammatory, In Controlling Intestinal Factors Contributing To Inflammatory Bowel Disease., Gerald Wayne Dryden, Jr.

Electronic Theses and Dissertations

This dissertation explores the role of epigallocatechin-3-gallate (EGCG), as a potential treatment for patients with inflammatory bowel disease (IBD). IBD is a common disorder that causes a great deal of suffering. Our understanding of the etiologies, pathogenic mechanisms, and treatment targets continues to evolve. Many new therapeutic targets are making their way through the pharmaceutical pipelines. However, not all patients benefit from these therapies. EGCG has long been studied as an anti-cancer agent. Most of our understanding of this compound comes from the oncologic literature. As the pathways of oncology and inflammation converge, new lessons can be taken from the …

Porphyromonas Gingivalis Gingipains Induce A Pro-Inflammatory Extracellular Microenvironment : The Role Of Par-2 And Fibronectin., Jeffrey S. Marschall

Electronic Theses and Dissertations

Periodontitis is a chronic inflammatory disease that is characterized by severe tissue destruction of the gingiva and other tooth supporting structures; if left untreated, tooth loss and disintegration of the alveolar bone occurs. This chronic inflammatory state has been linked to other systemic diseases such as cardiovascular disease, diabetes, rheumatoid arthritis, and Alzheimer’s disease. Porphyromonas gingivalis is the major pathogenic microbe in periodontitis. The main virulence factors of P. gingivalis are the Arg-aa and Lys-aa gingipains, which are proteolytic enzymes implicated in a plethora of activities that allow P. gingivalis to subvert the human immune system in the oral cavity …

Human Neonatal Fc Receptor Mediates Transcytosis Of Immunoglobulin-G-Bound Ovalbumin, Farah Gazi

MCB Articles

Introduction: There is increasing evidence that allergies, like many other chronic diseases of childhood, may have origins during the prenatal period. It is also known that mothers, have a stronger influence than fathers, on the development of allergic disease in their children. While the mechanisms responsible for this maternal influence are not known, studies have indicated the possibility of transplacental allergen transfer via immunoglobulin G (IgG) containing immune complexes.

Objective: In this study, we investigated the ability of the neonatal Fc receptor for IgG transport (FcRn) to bind and transport the model allergen ovalbumin in the form of an IgG-ovalbumin …

Regulation Of Irf-3-Dependent Innate Immune Signaling Pathway By The Plpro Domain Of Non-Structural Protein 3 (Nsp3) Of Severe Acute Respiratory Syndrome (Sars) Coronavirus, Sandra Nicole Lester

Theses and Dissertations (ETD)

The induction of Type I Interferons (IFNs) is a powerful and rapid innate defense mechanism against viral infection, and many viruses have developed elaborate strategies to overcome the antiviral effects of IFN, ensuring their survival and replication. Severe acute respiratory syndrome coronavirus (SARS-CoV) is a highly pathogenic virus that causes severe lung disease in humans and is associated with high mortality rates. SARS-CoV, like all other successful viruses, encode proteins that counteract the innate immune response. A number of reports have indicated the papain-like protease (PLpro) domain of SARS-CoV Non-Structural Protein 3 (NSP3) as a powerful interferon antagonist, by suppressing …

Pten Signaling In Regulatory T Cells And Inflammatory Disease, Sharad Krishna Shrestha

Theses and Dissertations (ETD)

Regulatory T (Treg) cells suppress CD4+ T cell responses during homeostasis and inflammation to prevent autoimmunity and other immune disorders. Although the transcriptional and epigenetic programs impacting Treg cell function have been extensively studied, the signaling and metabolic pathways underlying Treg stability and function are not fully understood. In this study, we determined the role of the phosphatase PTEN in Treg cells. We found that specific depletion of PTEN in Treg cells results in excessive TH1 and T follicular helper cells (TFH) responses, associated with elevated germinal center (GC) B cells and spontaneous development of autoimmune and lymphoproliferative disease in …