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Long Non-Coding Rna Lincrna-Eps Inhibits Host Defense Against Listeria Monocytogenes Infection, Federica Agliano, Katherine A. Fitzgerald, Anthony T. Vella, Vijay A. Rathinam, Andrei E. Medvedev 2020 University of Connecticut

Long Non-Coding Rna Lincrna-Eps Inhibits Host Defense Against Listeria Monocytogenes Infection, Federica Agliano, Katherine A. Fitzgerald, Anthony T. Vella, Vijay A. Rathinam, Andrei E. Medvedev

Open Access Articles

Long non-coding RNAs (lncRNAs) have emerged as key regulators of gene expression in several biological systems. The long intergenic RNA-erythroid pro-survival (lincRNA-EPS) has been shown to play a critical role in restraining inflammatory gene expression. However, the function of lincRNA-EPS during bacterial infections remains unknown. Here, we demonstrate that following infection with the intracellular bacterium Listeria monocytogenes, both mouse macrophages and dendritic cells lacking lincRNA-EPS exhibit an enhanced expression of proinflammatory cytokine genes, as well as an increased expression of the inducible nitric oxide synthase (iNos) and nitric oxide (NO) production. Importantly, we found that lincRNA-EPS(-/-) mice intraperitoneally infected with ...


Impact Of Th1 Cd4 Tfh Skewing On Antibody Responses To An Hiv-1 Vaccine In Rhesus Macaques, Anil Verma, Keith A. Reimann, David H. Foehl, Smita S. Iyer 2019 University of California, Davis

Impact Of Th1 Cd4 Tfh Skewing On Antibody Responses To An Hiv-1 Vaccine In Rhesus Macaques, Anil Verma, Keith A. Reimann, David H. Foehl, Smita S. Iyer

Open Access Articles

Generating durable humoral immunity through vaccination depends upon effective interaction of follicular helper T cells (Tfh) with germinal center (GC) B cells. Th1 polarization of Tfh cells is an important process shaping the success of Tfh-GC B cell interactions by influencing co-stimulatory and cytokine-dependent Tfh help to B cells. However, the question remains whether adjuvant-dependent modulation of Tfh cells enhances HIV-1 vaccine-induced anti-Envelope (Env) antibody responses. We investigated whether an HIV-1 vaccine platform designed to increase the number of Th1-polarized Tfh cells enhances the magnitude and quality of anti-Env antibodies. Utilizing a novel interferon-induced protein (IP)-10-adjuvanted HIV-1 DNA prime ...


Differential Skewing Of Donor-Unrestricted And Gammadelta T Cell Repertoires In Tuberculosis-Infected Human Lungs, Paul Ogongo, Adrie Jc. Steyn, Farina Karim, Kaylesh J. Dullabh, Ismael Awala, Rajhmun Madansein, Alasdair Leslie, Samuel M. Behar 2019 University of KwaZulu-Natal

Differential Skewing Of Donor-Unrestricted And Gammadelta T Cell Repertoires In Tuberculosis-Infected Human Lungs, Paul Ogongo, Adrie Jc. Steyn, Farina Karim, Kaylesh J. Dullabh, Ismael Awala, Rajhmun Madansein, Alasdair Leslie, Samuel M. Behar

Open Access Articles

Unconventional T cells that recognize mycobacterial antigens are of great interest as potential vaccine targets against tuberculosis (TB). This includes donor-unrestricted T cells (DURTs), such as mucosa-associated invariant T cells (MAITs), CD1-restricted T cells, and gammadelta T cells. We exploited the distinctive nature of DURTs and gammadelta T cell receptors (TCRs) to investigate the involvement of these T cells during TB in the human lung by global TCR sequencing. Making use of surgical lung resections, we investigated the distribution, frequency, and characteristics of TCRs in lung tissue and matched blood from individuals infected with TB. Despite depletion of MAITs and ...


A Novel Vaccine Platform Using Glucan Particles For Induction Of Protective Responses Against Francisella Tularensis And Other Pathogens, Ambily Abraham, Gary R. Ostroff, Stuart M. Levitz, P. C. F. Oyston 2019 University of Massachusetts Medical School

A Novel Vaccine Platform Using Glucan Particles For Induction Of Protective Responses Against Francisella Tularensis And Other Pathogens, Ambily Abraham, Gary R. Ostroff, Stuart M. Levitz, P. C. F. Oyston

Open Access Articles

Vaccines are considered the bedrock of preventive medicine. However, for many pathogens, it has been challenging to develop vaccines that stimulate protective, long-lasting immunity. We have developed a novel approach using beta-1,3-D-glucans (BGs), natural polysaccharides abundantly present in fungal cell walls, as a biomaterial platform for vaccine delivery. BGs simultaneously provide for receptor-targeted antigen delivery to specialized antigen-presenting cells together with adjuvant properties to stimulate antigen-specific and trained non-specific immune responses. This review focuses on various approaches of using BG particles (GPs) to develop bacterial and fungal vaccine candidates. A special case history for the development of an effective ...


Common Nodes Of Virus-Host Interaction Revealed Through An Integrated Network Analysis, Korbinian Bosl, Richard K. Kandasamy 2019 Norwegian University of Science and Technology

Common Nodes Of Virus-Host Interaction Revealed Through An Integrated Network Analysis, Korbinian Bosl, Richard K. Kandasamy

Open Access Articles

Viruses are one of the major causes of acute and chronic infectious diseases and thus a major contributor to the global burden of disease. Several studies have shown how viruses have evolved to hijack basic cellular pathways and evade innate immune response by modulating key host factors and signaling pathways. A collective view of these multiple studies could advance our understanding of virus-host interactions and provide new therapeutic perspectives for the treatment of viral diseases. Here, we performed an integrative meta-analysis to elucidate the 17 different host-virus interactomes. Network and bioinformatics analyses showed how viruses with small genomes efficiently achieve ...


Oral Administration Of An Anti-Cfae Secretory Iga Antibody Protects Against Enterotoxigenic Escherichia Coli Diarrheal Disease In A Non-Human Primate Model, Matteo Stoppato, Carlos Gaspar, James Regeimbal, Gladys Nunez, Serena Giuntini, Melissa A. Gawron, Jessica R. Pondish, Joseph C. Martin III, Matthew Schneider, Zachary A. Schiller, Mark S. Klempner, Lisa A. Cavacini, Yang Wang 2019 University of Massachusetts Medical School

Oral Administration Of An Anti-Cfae Secretory Iga Antibody Protects Against Enterotoxigenic Escherichia Coli Diarrheal Disease In A Non-Human Primate Model, Matteo Stoppato, Carlos Gaspar, James Regeimbal, Gladys Nunez, Serena Giuntini, Melissa A. Gawron, Jessica R. Pondish, Joseph C. Martin Iii, Matthew Schneider, Zachary A. Schiller, Mark S. Klempner, Lisa A. Cavacini, Yang Wang

University of Massachusetts Medical School Faculty Publications

Enterotoxigenic Escherichia coli (ETEC) is a leading cause of diarrhea-associated illness in developing countries. There is currently no vaccine licensed to prevent ETEC and the development of an efficacious prophylaxis would provide an intervention with significant impact. Recent studies suggested that effective protection could be achieved by inducing immunity to block colonization of ETEC. Here, we evaluated the efficacy of secretory (s) IgA2 and dimeric (d) IgA2 of an anti-colonization factor antigen antibody, 68-61, in the Aotus nancymaae non-human primate (NHP) ETEC challenge model via oral and parental delivery. Thirty-nine animals were distributed across 3 groups of 13, and challenged ...


Intravital Imaging In A Zebrafish Model Elucidates Interactions Between Mucosal Immunity And Pathogenic Fungi, Linda S. Archambault 2019 University of Maine

Intravital Imaging In A Zebrafish Model Elucidates Interactions Between Mucosal Immunity And Pathogenic Fungi, Linda S. Archambault

Electronic Theses and Dissertations

Candida yeasts are common commensals that can cause mucosal disease and life-threatening systemic infections. While many of the components required for defense against Candida albicans infection are well established, questions remain about how various host cells at mucosal sites assess threats and coordinate defenses to prevent normally commensal organisms from becoming pathogenic. Using two Candida species, C. albicans and C. parapsilosis, which differ in their abilities to damage epithelial tissues, we used traditional methods (pathogen CFU, host survival, and host cytokine expression) combined with high-resolution intravital imaging of transparent zebrafish larvae to illuminate host-pathogen interactions at the cellular level in ...


Alternative Splicing Regulates Stochastic Nlrp3 Activity, Florian Hoss, James L. Mueller, Francisca Rojas Ringeling, Juan F. Rodriguez-Alcazar, Rebecca Brinkschulte, Gerald Seifert, Rainer Stahl, Lori Broderick, Chris D. Putnam, Richard D. Kolodner, Stefan Canzar, Matthias Geyer, Hal M. Hoffman, Eicke Latz 2019 University of Bonn

Alternative Splicing Regulates Stochastic Nlrp3 Activity, Florian Hoss, James L. Mueller, Francisca Rojas Ringeling, Juan F. Rodriguez-Alcazar, Rebecca Brinkschulte, Gerald Seifert, Rainer Stahl, Lori Broderick, Chris D. Putnam, Richard D. Kolodner, Stefan Canzar, Matthias Geyer, Hal M. Hoffman, Eicke Latz

Open Access Articles

Leucine-rich repeat (LRR) domains are evolutionarily conserved in proteins that function in development and immunity. Here we report strict exonic modularity of LRR domains of several human gene families, which is a precondition for alternative splicing (AS). We provide evidence for AS of LRR domain within several Nod-like receptors, most prominently the inflammasome sensor NLRP3. Human NLRP3, but not mouse NLRP3, is expressed as two major isoforms, the full-length variant and a variant lacking exon 5. Moreover, NLRP3 AS is stochastically regulated, with NLRP3 exon 5 lacking the interaction surface for NEK7 and hence loss of activity. Our data thus ...


A Permethrin Metabolite Is Associated With Adaptive Immune Responses In Gulf War Illness, Utsav Joshi, Lawrence J. Stern, Laila Abdullah 2019 The Open University

A Permethrin Metabolite Is Associated With Adaptive Immune Responses In Gulf War Illness, Utsav Joshi, Lawrence J. Stern, Laila Abdullah

Open Access Articles

Gulf War Illness (GWI), affecting 30% of veterans from the 1991 Gulf War (GW), is a multi-symptom illness with features similar to those of patients with autoimmune diseases. The objective of the current work is to determine if exposure to GW-related pesticides, such as permethrin (PER), activates peripheral and central nervous system (CNS) adaptive immune responses. In the current study, we focused on a PER metabolite, 3-phenoxybenzoic acid (3-PBA), as this is a common metabolite previously shown to form adducts with endogenous proteins. We observed the presence of 3-PBA and 3-PBA modified lysine of protein peptides in the brain, blood ...


Iiv-6 Inhibits Nf-Kappab Responses In Drosophila, Cara C. West, Florentina Rus, Ying Chen, Anni Kleino, Monique Gangloff, Don B. Gammon, Neal S. Silverman 2019 University of Massachusetts Medical School

Iiv-6 Inhibits Nf-Kappab Responses In Drosophila, Cara C. West, Florentina Rus, Ying Chen, Anni Kleino, Monique Gangloff, Don B. Gammon, Neal S. Silverman

Neal Silverman

The host immune response and virus-encoded immune evasion proteins pose constant, mutual selective pressure on each other. Virally encoded immune evasion proteins also indicate which host pathways must be inhibited to allow for viral replication. Here, we show that IIV-6 is capable of inhibiting the two Drosophila NF-kappaB signaling pathways, Imd and Toll. Antimicrobial peptide (AMP) gene induction downstream of either pathway is suppressed when cells infected with IIV-6 are also stimulated with Toll or Imd ligands. We find that cleavage of both Imd and Relish, as well as Relish nuclear translocation, three key points in Imd signal transduction, occur ...


Control Of Antiviral Innate Immune Response By Protein Geranylgeranylation, Shigao Yang, Zhaozhao Jiang, Katherine A. Fitzgerald, Donghai Wang 2019 Duke University

Control Of Antiviral Innate Immune Response By Protein Geranylgeranylation, Shigao Yang, Zhaozhao Jiang, Katherine A. Fitzgerald, Donghai Wang

Katherine A. Fitzgerald

The mitochondrial antiviral signaling protein (MAVS) orchestrates host antiviral innate immune response to RNA virus infection. However, how MAVS signaling is controlled to eradicate virus while preventing self-destructive inflammation remains obscure. Here, we show that protein geranylgeranylation, a posttranslational lipid modification of proteins, limits MAVS-mediated immune signaling by targeting Rho family small guanosine triphosphatase Rac1 into the mitochondria-associated endoplasmic reticulum (ER) membranes (MAMs) at the mitochondria-ER junction. Protein geranylgeranylation and subsequent palmitoylation promote Rac1 translocation into MAMs upon viral infection. MAM-localized Rac1 limits MAVS' interaction with E3 ligase Trim31 and hence inhibits MAVS ubiquitination, aggregation, and activation. Rac1 also facilitates ...


Chemical Depletion Of Phagocytic Immune Cells In Anopheles Gambiae Reveals Dual Roles Of Mosquito Hemocytes In Anti-Plasmodium Immunity, Hyeogsun Kwon, Ryan C. Smith 2019 Iowa State University

Chemical Depletion Of Phagocytic Immune Cells In Anopheles Gambiae Reveals Dual Roles Of Mosquito Hemocytes In Anti-Plasmodium Immunity, Hyeogsun Kwon, Ryan C. Smith

Entomology Publications

Mosquito innate immunity is comprised of both cellular and humoral factors that provide protection from invading pathogens. Immune cells, known as hemocytes, have been intricately associated with these immune responses through direct roles in phagocytosis and immune signaling. Recent studies have implicated hemocytes as integral determinants of anti-Plasmodium immunity, yet little is known regarding the specific mechanisms by which hemocytes limit malaria parasite survival. With limited genetic tools to enable their study, we employed a chemical-based treatment widely used for macrophage depletion in mammalian systems for the first time in an invertebrate organism. Upon its application in Anopheles gambiae, we ...


Tethering Of Vesicles To The Golgi By Gmap210 Controls Lat Delivery To The Immune Synapse, Andres Ernesto Zucchetti, Laurence Bataille, Jean-Marie Carpier, Stephanie Dogniaux, Mabel San Roman-Jouve, Mathieu Maurin, Michael W. Stuck, Rosa M. Rios, Cosima T. Baldari, Gregory J. Pazour, Claire Hivroz 2019 PSL Research University

Tethering Of Vesicles To The Golgi By Gmap210 Controls Lat Delivery To The Immune Synapse, Andres Ernesto Zucchetti, Laurence Bataille, Jean-Marie Carpier, Stephanie Dogniaux, Mabel San Roman-Jouve, Mathieu Maurin, Michael W. Stuck, Rosa M. Rios, Cosima T. Baldari, Gregory J. Pazour, Claire Hivroz

Open Access Articles

The T cell immune synapse is a site of intense vesicular trafficking. Here we show that the golgin GMAP210, known to capture vesicles and organize membrane traffic at the Golgi, is involved in the vesicular transport of LAT to the immune synapse. Upon activation, more GMAP210 interact with LAT-containing vesicles and go together with LAT to the immune synapse. Regulating LAT recruitment and LAT-dependent signaling, GMAP210 controls T cell activation. Using a rerouting and capture assay, we show that GMAP210 captures VAMP7-decorated vesicles. Overexpressing different domains of GMAP210, we also show that GMAP210 allows their specific delivery to the immune ...


Cell-Free Dna Release During Programmed Cell Death In Ischemia Reperfusion Injury, Alexander Dionne, Anthony M. Jevnikar, Zhu-Xu Zhang 2019 The University of Western Ontario

Cell-Free Dna Release During Programmed Cell Death In Ischemia Reperfusion Injury, Alexander Dionne, Anthony M. Jevnikar, Zhu-Xu Zhang

Western Research Forum

Transplantation is invariably associated with acute allograft injury caused by ischemia reperfusion injury (IRI). This injury causes cells of the allograft to undergo various forms of programmed cell death including apoptosis and necroptosis. During programmed cell death, immunogenic molecules are released from cells, one of which is cell-free DNA (cfDNA). We hypothesize that cfDNA is released by microvascular endothelial cells (MVECs) during programmed cell death of IRI and that cfDNA acts as both a biomarker for cellular injury as well as a biologically active molecule capable of amplifying inflammation and organ injury.

Our results indicate that cfDNA is released by ...


The Fatty Acid Oleate Is Required For Innate Immune Activation And Pathogen Defense In Caenorhabditis Elegans, Sarah M. Anderson, Hilary K. Cheesman, Nicholas D. Peterson, Elisabeth B. Salisbury, Alexander A. Soukas, Read Pukkila-Worley 2019 University of Massachusetts Medical School

The Fatty Acid Oleate Is Required For Innate Immune Activation And Pathogen Defense In Caenorhabditis Elegans, Sarah M. Anderson, Hilary K. Cheesman, Nicholas D. Peterson, Elisabeth B. Salisbury, Alexander A. Soukas, Read Pukkila-Worley

Open Access Articles

Fatty acids affect a number of physiological processes, in addition to forming the building blocks of membranes and body fat stores. In this study, we uncover a role for the monounsaturated fatty acid oleate in the innate immune response of the nematode Caenorhabditis elegans. From an RNAi screen for regulators of innate immune defense genes, we identified the two stearoyl-coenzyme A desaturases that synthesize oleate in C. elegans. We show that the synthesis of oleate is necessary for the pathogen-mediated induction of immune defense genes. Accordingly, C. elegans deficient in oleate production are hypersusceptible to infection with diverse human pathogens ...


A Novel Phox/Cd38/Mcoln1/Tfeb Axis Important For Macrophage Activation During Bacterial Phagocytosis, Mehran Najibi, Joseph A. Moreau, Havisha H. Honwad, Javier E. Irazoqui 2019 University of Massachusetts Medical School

A Novel Phox/Cd38/Mcoln1/Tfeb Axis Important For Macrophage Activation During Bacterial Phagocytosis, Mehran Najibi, Joseph A. Moreau, Havisha H. Honwad, Javier E. Irazoqui

University of Massachusetts Medical School Faculty Publications

Macrophages are a key and heterogenous class of phagocytic cells of the innate immune system, which act as sentinels in peripheral tissues and are mobilized during infection. Macrophage activation in the presence of bacterial cells and molecules entails specific and complex programs of gene expression. How such triggers elicit the gene expression programs is incompletely understood. We previously discovered that transcription factor TFEB is a key contributor to macrophage activation during bacterial phagocytosis. However, the mechanism linking phagocytosis of bacterial cells to TFEB activation remained unknown. In this article, we describe a previously unknown pathway that links phagocytosis with the ...


Nf-Κb In Biomphalaria Glabrata: A Genetic Fluke?, Paige Stocker 2019 Lawrence University

Nf-Κb In Biomphalaria Glabrata: A Genetic Fluke?, Paige Stocker

Lawrence University Honors Projects

Biomphalaria glabrata is the intermediate host to the disease causing parasitic worm, Schistosoma mansoni. Previous work has identified homologs of NF-κB, a known immune related transcription factor, in B. glabrata and work has also been done to establish putative κB sites. It has also been observed that the p65 homologous subunit has an extended N-terminal region not present in other homologs. The goal of the present study is twofold: investigate DNA binding affinity of two NF-κB subunits, Bg-p65 and Bg-p50, and characterize the nature of the N-terminal extension of Bg-p65. In the current work, it is shown through the use ...


Control Of Antiviral Innate Immune Response By Protein Geranylgeranylation, Shigao Yang, Zhaozhao Jiang, Katherine A. Fitzgerald, Donghai Wang 2019 Duke University

Control Of Antiviral Innate Immune Response By Protein Geranylgeranylation, Shigao Yang, Zhaozhao Jiang, Katherine A. Fitzgerald, Donghai Wang

Open Access Articles

The mitochondrial antiviral signaling protein (MAVS) orchestrates host antiviral innate immune response to RNA virus infection. However, how MAVS signaling is controlled to eradicate virus while preventing self-destructive inflammation remains obscure. Here, we show that protein geranylgeranylation, a posttranslational lipid modification of proteins, limits MAVS-mediated immune signaling by targeting Rho family small guanosine triphosphatase Rac1 into the mitochondria-associated endoplasmic reticulum (ER) membranes (MAMs) at the mitochondria-ER junction. Protein geranylgeranylation and subsequent palmitoylation promote Rac1 translocation into MAMs upon viral infection. MAM-localized Rac1 limits MAVS' interaction with E3 ligase Trim31 and hence inhibits MAVS ubiquitination, aggregation, and activation. Rac1 also facilitates ...


Stalking Flu: Development And Characterization Of A Broadly Neutralizing Monoclonal Antibody Targeting The Influenza Hemagglutinin Stem, Elizabeth Newman 2019 Touro College and University System

Stalking Flu: Development And Characterization Of A Broadly Neutralizing Monoclonal Antibody Targeting The Influenza Hemagglutinin Stem, Elizabeth Newman

NYMC Student Theses and Dissertations

Seasonal epidemics caused by influenza A viruses (IAV) result in an estimated 290,000- 650,000 deaths worldwide each year (17). While antivirals targeted to influenza exist, resistance to these drugs is increasing and regular vaccination remains the most effective way to prevent infection (26, 73, 99). However due to the persistence of antigenic drift and shift, influenza vaccines must be updated each season and antigenic mismatches can reduce efficacy (24, 118). Immunity to influenza either from vaccination or infection is principally mediated by antibodies generated to one of its major surface proteins, Hemagglutinin (HA). HA is a homotrimer, each ...


A Mathematical Investigation On Tumor-Immune Dynamics: The Impact Of Vaccines On The Immune Response, Jonathan Quinonez, Neethi Dasu, Mahboobi Qureshi 2019 Larkin Hospital (Florida)

A Mathematical Investigation On Tumor-Immune Dynamics: The Impact Of Vaccines On The Immune Response, Jonathan Quinonez, Neethi Dasu, Mahboobi Qureshi

Stratford Campus Research Day

Mathematical models analyzing tumor-immune interactions provide a framework by which to address specific scenarios in regard to tumor-immune dynamics. Important aspects of tumor-immune surveillance to consider is the elimination of tumor cells from a host’s cell-mediated immunity as well as the implications of vaccines derived from synthetic antigen. In present studies, our mathematical model examined the role of synthetic antigen to the strength of the immune system. The constructed model takes into account accepted knowledge of immune function as well as prior work done by de Pillis et al. All equations describing tumor-immune growth, antigen presentation, immune response, and ...


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