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Psychosocial Distress Mediates Immune Dysregulation Through Alterations In Global Epigenetic Patterns And Chromatin Remodeling Proteins, Karen Krukowski

Dissertations

Psychosocial distress, characterized by increased perceived stress, anxiety and mood disturbance, is a common response of women to a diagnosis of breast cancer (Northouse, 1992; Pettingale et al., 1988; Stark and House, 2000; Witek-Janusek et al., 2007). This psychosocial distress leads to activation of the hypothalamic-pituitary-adrenocortical (HPA) axis and increased circulating glucocorticoids (GCs) (Chrousos, 2000; Chrousos and Gold, 1992; Schoneveld and Cidlowski, 2007). Increased psychosocial distress and increased HPA activation can lead to immune dysregulation consisting of reduced natural killer (NK) cell activity (NKCA) (Biondi, 2001; Kiecolt-Glaser et al., 1987; Kiecolt-Glaser et al., 2002; Witek-Janusek et al., 2008; Witek-Janusek et …

Characterization Of Chronic Glucocorticoid Exposure On Natural Killer Cell Function: A Model For Stress Induced Alterations On The Epigenetic Landscape, Justin Lee Eddy

Dissertations

Psychological stress can impact immune function through altered glucocorticoid production. Natural killer (NK) cells and their effector functions are particularly susceptible to both psychological stress as well as exogenous glucocorticoids. The purpose of this study was to assess the impact of chronic glucocorticoid (GC) exposure on NK cells to investigate the immune dysregulation associated with periods of psychological stress.

Chronic in vitro treatment of the NK92 cell line produced a dichotomous NK phenotype with enhanced proinflammatory cytokine production yet reduced NK cell lytic activity (NKCA). This dichotomy was at the individual cell level where mRNA and protein levels for proinflammatory …

Ex Vivo Induction Of Human Regulatory T Cells, Kathleen Elizabeth Jaeger

Dissertations

Regulatory T cells (Tregs) are indispensable in the human immune system in the maintenance of self-tolerance and immune homeostasis. The dysregulation of Treg number and/or function plays a critical role in the pathogenesis of cancer, allergy and human autoimmune pathologies such as multiple sclerosis, psoriasis, rheumatoid arthritis and diabetes. The primary aim of this research was to determine the molecular mechanisms and cellular interactions which promote human Treg induction. From umbilical cord blood (UCB) samples, we found that antigen receptor stimulation of UCB T cells via a CD14+ monocyte population leads to a predominant induction of Tregs.

Further studies identified …

Defining A Role For Inducible Heat Shock Protein 70 (Hsp70i) In Mediating Autoimmune Vitiligo, Jeffrey Alan Mosenson

Dissertations

Vitiligo is an autoimmune disease characterized by destruction of melanocytes, leaving 0.5% of the population with progressive depigmentation. Current treatments offer limited efficacy. Observations that heat shock proteins (HSPs) can serve as adjuvants in antitumor vaccines first suggested to us a link between HSPs and stress-induced vitiligo. Such proteins are marvelously well conserved throughout evolution, which has placed them in the spotlight for helping to understand the intriguing relationship between infection and immunity. Intracellularly, inducible heat shock protein 70 (HSP70i) is upregulated by stress and helps protect cells from undergoing apoptosis. In times of stress, melanocytes will secrete antigen bound …

Evidence For Renewal And Reconstitution Of Marginal Zone Macrophages In Young And Aged Mice, Erika Bahamon

Master's Theses

Aging in humans and mice correlates with decline in immune health, affecting both innate and adaptive immunity. Response against blood-borne bacterial pathogens is compromised because of the deterioration of the marginal zones of the spleen and decrease in frequency of marginal zone macrophages (MZM). This thesis asked if low cell turnover is the cause for the decrease of MZM, using cell proliferation to indicate cell turnover in spleens of mice. First, evidence showed MZM proliferation occurred in spleens of young mice and was decreased in the MZM from aged mice. Second, transfer of young bone marrow into old mice replenished …

Characterization Of Inducible Regulatory T Cells: An Umbilical Cord Blood Model, Rebecca Anne Krier

Master's Theses

The immune system is a group of structures and processes that protect us from disease. To function properly it must recognize a wide variety of pathogens such as viruses and bacteria. T cells play a crucial role in an immune response; however, an overactive immune response can lead to autoimmune diseases, therefore it is important that the immune system has the ability to negatively regulate an immune response. In the periphery, regulatory T cells (CD4⁺CD25⁺Foxp3⁺) are involved in the maintenance of self-tolerance and immune homeostasis. Mechanisms involved in the induction of iTregs from naïve …

Selective Expansion Of B Cells By Intestinal Microbiota, Karina Ochoa

Master's Theses

In rabbits, antibody diversity and B cell expansion are generated in gut-associated lymphoid tissues (GALT), in an antigen- and T cell-independent mechanism, and require interaction with intestinal microbiota. I investigated, in vitro, the mechanism by which commensals drive GALT reactions. Bacteria were isolated from the GALT of rabbits and identified by 16sRNA sequencing. I found that the commensals can bind to Ig, independently of their specificity. In addition, a ~20kDa bacterial molecule was immunoprecipitated with recombinant Ig molecules. Stimulation of B cells with selected bacterial molecules induced the activation of B cells. Stimulation of B cells through TLR2 induced the …

The Inflammatory Response Initiated By The Spleen To Ischemic Stroke, Hilary Seifert

USF Tampa Graduate Theses and Dissertations

The peripheral immune system plays a role in delayed neural injury after stroke. This response originates from the spleen as splenectomy prior to middle cerebral artery occlusion (MCAO) in rats significantly reduces infarct volume in the brain. This research is based on the hypothesis that inhibiting the splenic response will reduce neurodegeneration after stroke. Studies in animals have implicated lymphocytes as the immune cell type that is detrimental following MCAO. Interferon gamma (IFNγ) has been identified as a pro-inflammatory cytokine that is also detrimental following stroke. IFNγ is important because it activates microglia and macrophages in a pro-inflammatory nature that …

Prenatal Stress, Depression, And Herpes Viral Titers, Pao-Chu Hsu

USF Tampa Graduate Theses and Dissertations

Recent studies suggest that some cases of prenatal depression may be associated with reactivation of latent infections of the herpesvirus family. The possible relationships among stress, prenatal depression, and herpes viral reactivation in pregnancy are understudied and the molecular pathways such as the neuroimmune biogenic amine pathway are unidentified. Chronic stress shifts the T helper-1 cell (Th1) cytokine profile to a Th2 profile, which favors virus induced pathogenesis and survival. Pregnancy is also associated with a similar Th2 dominance. In non-pregnant individuals, exposure to psychological or physical stress may be associated with latent herpes viral reactivation and could result in …

Phenotypic And Genotypic Analysis Of In Vitro Selected Miltefosine Resistant Leishmania Donovani, Brian A. Vesely

USF Tampa Graduate Theses and Dissertations

Abstract

Visceral leishmaniasis is a devastating neglected parasitic disease caused by infection with Leishmania donovani. It life cycle has two stages with promastigote (insect stage) and amastigote (animal stage) morphologies. Miltefosine is currently the only commercially available oral drug available to treat leishmaniasis and recent evidence suggests clinical resistance has emerged. Due to the importance of this drug and the scarcity of new drugs in the pipeline, work has been done on understanding the mechanism(s) of miltefosine, yet the mechanism of action for resistance is still not known.

In previous studies investigators generated miltefosine resistance on the insect vector stage …

Epigenetic Modifiers To Augment The Immunogenicity Of Chronic Lymphocytic Leukemia, Jason A. Dubovsky

USF Tampa Graduate Theses and Dissertations

Cancer cells employ a litany of immunosuppressive and immunevasive strategies to avoid detection and elimination by the various arms of the innate and adaptive immune system. Many hematologic and solid tumors progressively develop a specialized microenvironment which promotes tissue restructuring inflammation while masking the immune signature of the tumor cells themselves. Chronic lymphocytic leukemia, a malignancy of mature B lymphocytes must constantly balance on the precipice of immune recognition. A mature antigen presenting cell themselves, CLL clonal growth is dependent on the very interactions which, if effective, could potentially lead to their demise. To circumvent this, CLL clones set up …

Worms, Nematoda, Scott Lyell Gardner

Scott L. Gardner Publications

Nematodes are the most speciose phylum of metazoa on earth. Not only do they occur in huge numbers as parasites of all known animal groups, but also they are found in the soils, as parasites of plants, and in large numbers in the most extreme environments, from the Antarctic dry valleys to the benthos of the ocean. They are extremely variable in their morphological characteristics, with each group showing morphological adapta­tions to the environment that they inhabit. Soil-dwelling forms are extremely small; many marine species have long and complex setae; and parasitic species man­ifest amazingly great reproductive potential and large …

Influence Of Therapeutic Ceftiofur Treatments Of Feedlot Cattle On Fecal And Hide Prevalences Of Commensal Escherichia Coli Resistant To Expanded-Spectrum Cephalosporins, And Molecular Characterization Of Resistant Isolates, John W. Schmidt, Dee Griffin, Larry A. Kuehn, Dayna M. Brichta-Harhay

School of Veterinary and Biomedical Sciences: Faculty Publications

In the United States, the bla_CMY-2 gene contained within incompatibility type A/C (IncA/C) plasmids is frequently identified in extended-spectrum-cephalosporin-resistant (ESC^r) Escherichia coli strains from both human and cattle sources. Concerns have been raised that therapeutic use of ceftiofur in cattle may increase the prevalence of ESC^r E. coli. We report that herd ESC^r E. coli fecal and hide prevalences throughout the residency of cattle at a feedlot, including during the period of greatest ceftiofur use at the feedlot, were either not significantly different (P≥0.05) or significantly less (Pr E. coli shedding that follows ceftiofur …

Complete Closed Genome Sequences Of Mannheimia Haemolytica Serotypes A1 And A6, Isolated From Cattle, Gregory P. Harhay, Sergey Koren, Adam M. Phillippy, D. Scott Mcvey, Jennifer Kuszak, Michael L. Clawson, Dayna M. Harhay, Michael P. Heaton, Carol G. Chitko-Mckown, Timothy P. L. Smith

School of Veterinary and Biomedical Sciences: Faculty Publications

Mannheimia haemolytica is a respiratory pathogen affecting cattle and related ruminants worldwide. M. haemolytica is commonly associated with bovine respiratory disease complex (BRDC), a polymicrobial multifactorial disease.Wepresent the first two complete closed genome sequences of this species, determined using an automated assembly pipeline requiring no manual finishing.

Development And Evaluation Of A Replicon Particle Vaccine Expressing The E2 Glycoprotein Of Bovine Viral Diarrhea Virus (Bvdv) In Cattle, John Dustin Loy, Jill Gander, Mark Mogler, Ryan Vander Veen, Julia Ridpath, Delbert Hank Harris, Kurt Kamrud

School of Veterinary and Biomedical Sciences: Faculty Publications

Background: Bovine viral diarrhea virus is one of the most significant and costly viral pathogens of cattle worldwide. Alphavirus-derived replicon particles have been shown to be safe and highly effective vaccine vectors against a variety of human and veterinary pathogens. Replicon particles are non-propagating, DIVA compatible, and can induce both humoral and cell mediated immune responses. This is the first experiment to demonstrate that Alphavirus-based replicon particles can be utilized in a standard prime/boost vaccination strategy in calves against a commercially significant bovine pathogen.

Findings: Replicon particles that express bovine viral diarrhea virus sub-genotype 1b E2 glycoprotein were …

A Dysfunctional Tricarboxylic Acid Cycle Enhances Fitness Of Staphylococcus Epidermidis During Β-Lactam Stress, Vinai Chittenzham Thomas, Lauren Kinkhead, Ashley Janssen, Carolyn Schaeffer, Keith Woods, Jill Lindgren, Johnathan Peaster, Sujata Chaudhari, Marat Sadykov, Joselyn Jones, Sameh Mohamadi Abdelghani, Matthew Zimmerman, Kenneth W. Bayles, Greg Somerville, Paul Fey

School of Veterinary and Biomedical Sciences: Faculty Publications

A recent controversial hypothesis suggested that the bactericidal action of antibiotics is due to the generation of endogenous reactive oxygen species (ROS), a process requiring the citric acid cycle (tricarboxylic acid [TCA] cycle). To test this hypothesis, we assessed the ability of oxacillin to induce ROS production and cell death in Staphylococcus epidermidis strain 1457 and an isogenic citric acid cycle mutant. Our results confirm a contributory role for TCA-dependent ROS in enhancing susceptibility of S. epidermidis toward β-lactam antibiotics and also revealed a propensity for clinical isolates to accumulate TCA cycle dysfunctions presumably as a way to tolerate these …

Interferon Inducible Protein Ifi35 Negatively Regulates Rig-I Antiviral Signaling And Supports Vesicular Stomatitis Virus Replication, Anshuman Das, Phat X. Dinh, Debasis Panda, Asit K. Pattnaik

School of Veterinary and Biomedical Sciences: Faculty Publications

In a genome-wide siRNA screen, we recently identified the interferon (IFN) inducible protein 35 (IFI35, also known as IFP35) as a factor required for VSV infection. Studies reported here were conducted to further understand the role and requirement of IFI35 in VSV infection. Consistent with the siRNA screening data, we found that depletion of IFI35 led to reduced VSV replication at the level of viral gene expression. Although no direct interaction of IFI35 with the viral replication machinery was observed, we found that IFI35 negatively regulated the host innate immune response and rescued poly(I:C)-induced inhibition of VSV replication. Promoter-driven reporter …

Characterization Of A Serologic Marker Candidate For Development Of A Live-Attenuated Diva Vaccine Against Porcine Reproductive And Respiratory Syndrome Virus, Hiep Vu, Byungjoon Kwon, Marcelo De Lima, Asit K. Pattnaik, Fernando A. Osorio

School of Veterinary and Biomedical Sciences: Faculty Publications

DIVA (differentiating infected from vaccinated animals) vaccines have proven extremely useful for control and eradication of infectious diseases in livestock. We describe here the characterization of a serologic marker epitope, so-called epitope-M201, which can be a potential target for development of a live-attenuated DIVA vaccine against porcine reproductive and respiratory syndrome virus (PRRSV). Epitope-M201 is located at the carboxyl terminus (residues 161-174) of the viral M protein. The epitope is highly immunodominant and well-conserved among type-II PRRSV isolates. Rabbit polyclonal antibodies prepared against this epitope are non-neutralizing; thus, the epitope does not seem to contribute to the protective immunity against …

Trex1 Regulates Lysosomal Biogenesis And Interferon-Independent Activation Of Antiviral Genes, Maroof Hasan, James Koch, Dinesh Rakheja, Asit K. Pattnaik, James Brugarolas, Igor Dozmorov, Beth Levine, Edward K. Wakeland, Min Ae Lee-Kirsch, Nan Yan

School of Veterinary and Biomedical Sciences: Faculty Publications

Innate immune sensing of viral nucleic acids triggers type I interferon (IFN) production, which activates interferon-stimulated genes (ISGs) and directs a multifaceted antiviral response. ISGs can also be activated through IFN-independent pathways, although the precise mechanisms remain elusive. Here we found that the cytosolic exonuclease Trex1 regulates the activation of a subset of ISGs independently of IFN. Both Trex1−/− mouse and TREX1-mutant human cells express high levels of antiviral genes and are refractory to viral infections. The IFN-independent activation of antiviral genes in Trex1−/− cells requires STING, TBK1 and IRF3 and IRF7. We also found that Trex1-deficient cells display expanded …

Glutaredoxin-2 Is Required To Control Proton Leak Through Uncoupling Protein-3, Ryan J. Mailloux, Jian Ying Xuan, Brittany Beauchamp, Marjorie F. Lou, Mary-Ellen Harper

School of Veterinary and Biomedical Sciences: Faculty Publications

Glutathionylation has emerged as a key modification required for controlling protein function in response to changes in cell redox status. Recently, we showed that the glutathionylation state of uncoupling protein-3 (UCP3) modulates the leak of protons back into the mitochondrial matrix, thus controlling reactive oxygen species production. However, whether or not UCP3 glutathionylation is mediated enzymatically has remained unknown because previous work relied on the use of pharmacological agents, such as diamide, to alter the UCP3 glutathionylation state. Here, we demonstrate that glutaredoxin-2 (Grx2), a matrix oxidoreductase, is required to glutathionylate and inhibit UCP3. Analysis of bioenergetics in skeletal muscle …

Sequence-Optimized And Targeted Double-Stranded Rna As A Therapeutic Antiviral Treatment Against Infectious Myonecrosis Virus In Litopenaeus Vannamei, J. Dustin Loy, Duan S. Loy, Mark A. Mogler, Bruce Janke, Kurt Kamrud, D. L. Hank Harris, Lyric C. Bartholomay

School of Veterinary and Biomedical Sciences: Faculty Publications

Infectious myonecrosis virus (IMNV) is a significant and emerging pathogen that has a tremendous impact on the culture of the Pacific white shrimp Litopenaeus vannamei. IMNV first emerged in Brazil in 2002 and subsequently spread to Indonesia, causing large economic losses in both countries. No existing therapeutic treatments or effective interventions currently exist for IMNV. RNA interference (RNAi) is an effective technique for preventing viral disease in shrimp. Here, we describe the efficacy of a double-stranded RNA (dsRNA) applied as an antiviral therapeutic following virus challenge. The antiviral molecule is an optimized dsRNA construct that targets an IMNV sequence …

A New Species Of Metathelazia (Nematoda: Pneumospiruridae) From The Lungs Of A Nine-Banded Armadillo In Central Mexico = Especie Nueva De Metathelazia (Nematoda: Pneumospiruridae) De Los Pulmones De Un Armadillo Del Centro De México, F. Agustín Jiménez-Ruiz, Rogelio Rosas-Valdez, Scott Lyell Gardner

Harold W. Manter Laboratory of Parasitology: Faculty Publications

Twenty-four worms were collected from the bronchioles in both lungs of a male nine-banded armadillo Dasypus novemcinctus Linnaeus, 1758 captured in Teacalco, Morelos, Mexico. The worms, herein named Metathelazia mexicana n. sp., show a constriction in the esophagus at the level of the nerve ring; males of the species have 7 pairs of papillae, fewer than the other species in the genus. Metathelazia capsulata is the most similar species to Metathelazia mexicana; however, the latter has much shorter spicules. This is the fourth species in the genus known to occur in the New World.

Se recolectó un total de …

On The Morphology And Taxonomy Of Griphobilharzia Amoena Platt And Blair, 1991 (Schistosomatoidea), A Dioecious Digenetic Trematode Parasite Of The Freshwater Crocodile, Crocodylus Johnstoni, In Australia [Critical Comment], Thomas R. Platt, Eric P. Hoberg, Leslie A. Chisholm

Harold W. Manter Laboratory of Parasitology: Faculty Publications

Griphobilharzia amoena Platt and Blair, 1991 was originally described was originally described as a dioecious trematode, parasitic in the circulatory system of the Australian freshwater crocodile, Crocodylus johnstoni, with the female completely enclosed in a gynecophoric chamber of the male and the two worms orientated anti-parallel to each other. A recent publication questions the original description, arguing that G. amoena is monoecious and, as a consequence, the species was transferred to Vasotrema Stunkard, 1928 (Spirorchiidae) as Vasotrema amoena n. comb. We provide photomicrographic evidence that the original description of G. amoena is correct and that Griphobilharzia Platt and Blair, …

Dirofilariosis In The Americas: A More Virulent Dirofilaria Immitis?, Filipe Dantas-Torres, Domenico Otranto

Harold W. Manter Laboratory of Parasitology: Library Materials

Dirofilarioses are widespread diseases caused by filarioid nematodes (superfamily Filarioidea) of the genus Dirofilaria, which are transmitted by a plethora of mosquito species. The principal agent of canine dirofilariosis in the Americas is Dirofilaria immitis, which may also occasionally infest humans, resulting in pulmonary nodules that may be confounded with malignant lung tumours. Because human cases of dirofilariosis by D. immitis are relatively frequent in the Americas and rare in Europe and other eastern countries, where Dirofilaria repens is the main causative agent, the existence of a more virulent strain of D. immitis in the Americas …

The Role Of P38 Mapk In The Aetiopathogenesis Of Psoriasis And Psoriatic Arthritis, Athanasios Mavropoulos, Eirini I. Rigopoulou, Christos Liaskos, Dimitrios P. Bogdanos, Lazaros I. Sakkas

Biological Sciences Faculty Publications

The pathogenetic mechanisms responsible for the induction of immune-mediated disorders, such as psoriasis, remain not well characterized. Molecular signaling pathways are not well described in psoriasis, as well as psoriatic arthritis, which is seen in up to 40% of patients with psoriasis. Signaling pathway defects have long been hypothesized to participate in the pathology of psoriasis, yet their implication in the altered psoriatic gene expression still remains unclear. Emerging data suggest a potential pathogenic role for mitogen activated protein kinases p38 (p38 MAPK) extracellular signal-regulated kinase 1/2 (ERK1/2), and c-Jun N-terminal kinase (JNK) in the development of psoriasis. The data …

The Molecular Basis Of Antibody Mediated Neutralization Of Hepatitis C Virus, Michelle Catherine Sabo

All Theses and Dissertations (ETDs)

Hepatitis C virus: HCV) is positive strand, blood-borne, hepatotropic RNA virus that causes chronic infection in ~170 million people worldwide and is the leading cause of liver transplantation in the United States. HCV entry and attachment is mediated by the envelope protein E2 through interaction with several cellular receptors including CD81, scavenger receptor B1: SRB-1), claudin-1, and occludin, although the exact mechanism by which these receptors facilitate infection remains unclear, largely due to the absence of a structural model of E2. The production of neutralizing antibodies against E2 is thought to be important for controlling HCV infection, likely by blocking …

Validation Of N-Myristoyltransferase As Potential Chemotherapeutic Target In Chagas Disease, Linda Herrera

Open Access Theses & Dissertations

The protozoan parasite Trypanosoma cruzi is the etiological agent of Chagas disease, a problem endemic to Central and South America. In recent years, this neglected infectious disease has become a global health concern. The only clinically available drugs for the chemotherapy of Chagas disease have important disadvantages such as, high toxicity, strain resistance and variable efficacy. Therefore, there is an urgent need for the development of new antichagasic agents. The enzyme N-myristoyltransferase (NMT) has been characterized in a range of eukaryotes, from Saccharomyces cerevisae to Homo sapiens. Moreover, NMT has been shown to be essential in protozoan parasites, including Leishmania …

Mucin Associated Surface Protein Synthetic Peptide As A Novel Vaccine Candidate Against Chagas Disease, Carylinda Serna

Open Access Theses & Dissertations

Trypanosoma cruzi is an intracellular protozoan parasite and the etiological agent for Chagas disease. Chagas is endemic in Latin America affecting 18-20 million people. However, currently worldwide increasing numbers of the disease are being seen due to migration and globalization. This neglected disease causes significant morbidity, mortality, and an economic burden. There are no known vaccines and the only currently available drug is Benznidazole, but its effects are controversial. Nonetheless, a therapeutic or prophylactic vaccine is of urgent need to alleviate this disease. In this study we present an experimental approach using a synthetic peptide-based vaccine against T. cruzi. The …

Correlates Of Consistent Condom Use Among Female Entertainment Workers In Shanghai, China: A Repeated Measures Analysis, Xiushi Yang, Guomei Xia

Sociology & Criminal Justice Faculty Publications

Female entertainment workers (FEWs) in China are at increased risk of HIV and other sexually transmitted infections, but correlates of their risky sexual behaviour remain poorly understood. Using data from a series of four surveys, this paper employs repeated measures analysis to identify individual and social correlates of consistent condom use among FEWs in Shanghai. Results reveal that both individual cognitive and social influence factors are statistically significant in their bivariate relationships to consistent condom use with a stable or non-stable partner; only prevention motivation and perceived self-efficacy in condom use remain significant in the multiple regressions. When individual and …

Measuring Population Transmission Potential For Hiv: An Alternative Metric Of Transmission Risk In Men Who Have Sex With Men (Msm) In The Us, Colleen F. Kelley, Eli S. Rosenberg, Brandon M. O'Hara, Paula M. Frew, Travis Sanchez, John L. Peterson, Carlos Del Rio, Patrick S. Sullivan

Environmental & Global Health Faculty Research

Background Various metrics for HIV burden and treatment success [e.g. HIV prevalence, community viral load (CVL), population viral load (PVL), percent of HIV-positive persons with undetectable viral load] have important public health limitations for understanding disparities. Methods and Findings Using data from an ongoing HIV incidence cohort of black and white men who have sex with men (MSM), we propose a new metric to measure the prevalence of those at risk of transmitting HIV and illustrate its value. …See full text for complete abstract.