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Determining The Roles Of Dendritic Cells And Icam-1 In The Transpresentation Of Il-15 To Cd8 T Cells, Spencer W. Stonier

Dissertations and Theses (Open Access)

The maintenance and generation of memory CD8 T cells is dependent on the cytokine IL-15. IL-15 is delivered by a novel mechanism termed transpresentation: IL-15 is presented by a cell expressing IL-15Ralpha to the CD8 T cell which responds via IL-2Rbeta/gamma_c. The identity of what cells transpresent IL-15 to support the survival and homeostatic proliferation of memory CD8 T cells is unknown. Using a transgenic mouse model that limits IL-15 transpresentation to DCs, I have demonstrated that DCs transpresent IL-15 to CD8 T cells. DCs transpresent IL-15 to CD8 T cells during the contraction of an immune response …

Extracellular Atp Acts On P2y2 Purinergic Receptors To Facilitate Hiv-1 Infection, Claire Séror, Marie-Therese Melki, Frederic Subra, Syed Qasim Raza, Marlene Bras, Hela Saïdi, Roberta Nardacci, Laurent Voisin, Audrey Paoletti, Frederic Law, Isabelle Martins, Alessandra Amendola, Ali A. Abdul-Sater, Fabiola Ciccosanti, Olivier Delelis, Florence Niedergang, Sylvain Thierry, Najwane Said-Sadier, Christophe Lamaze, Didier Métivier, Jerome Estaquier, Gian Maria Fimia, Laura Falasca, Rita Casetti, Nazanine Modjtahedi, Jean M. Kanellopoulos, Jean-Francois Mouscadet, David M. Ojcius, Mauro Piacentini, Marie-Lise Gougeon, Guido Kroemer, Jean-Luc Perfetini

All Dugoni School of Dentistry Faculty Articles

Extracellular adenosine triphosphate (ATP) can activate purinergic receptors of the plasma membrane and modulate multiple cellular functions. We report that ATP is released from HIV-1 target cells through pannexin-1 channels upon interaction between the HIV-1 envelope protein and specific target cell receptors. Extracellular ATP then acts on purinergic receptors, including P2Y2, to activate proline-rich tyrosine kinase 2 (Pyk2) kinase and transient plasma membrane depolarization, which in turn stimulate fusion between Env-expressing membranes and membranes containing CD4 plus appropriate chemokine co-receptors. Inhibition of any of the constituents of this cascade (pannexin-1, ATP, P2Y2, and Pyk2) impairs the replication of HIV-1 mutant …

Determining The Roles Of Dendritic Cells And Icam-1 In The Transpresentation Of Il-15 To Cd8 T Cells, Spencer W. Stonier

Dissertations and Theses (Open Access)

The maintenance and generation of memory CD8 T cells is dependent on the cytokine IL-15. IL-15 is delivered by a novel mechanism termed transpresentation: IL-15 is presented by a cell expressing IL-15Ralpha to the CD8 T cell which responds via IL-2Rbeta/gamma_c. The identity of what cells transpresent IL-15 to support the survival and homeostatic proliferation of memory CD8 T cells is unknown. Using a transgenic mouse model that limits IL-15 transpresentation to DCs, I have demonstrated that DCs transpresent IL-15 to CD8 T cells. DCs transpresent IL-15 to CD8 T cells during the contraction of an immune response …

Enforced Expression Of Tbx1 In Fetal Thymic Epithelial Cells Antagonizes Thymus Organogenesis, Kim T. Cardenas

Dissertations and Theses (Open Access)

Enforced expression of Tbx1 in fetal thymic epithelial cells antagonizes

thymus organogenesis

Kim T. Cardenas

The thymus and parathyroid glands originate from organ-specific domains of 3rd pharyngeal pouch (PP) endoderm. At embryonic day 11.5 (E11.5), the ventral thymus and dorsal parathyroid domains can be identified by Foxn1 and Gcm2 expression respectively. Neural crest cells, (NCCs) play a role in regulating patterning of 3rd PP endoderm. In addition, pharyngeal endoderm influences fate determination via secretion of Sonic hedgehog (Shh), a morphogen required for Gcm2 expression and generation of the parathyroid domain. Gcm2 is a downstream target of the transcription factor Tbx1, …

Stat3 Controls The Neutrophil Migratory Response To Cxcr2 And Its Ligand Mip-2 (Cxcl2), Hoainam Nguyen-Jackson

Dissertations and Theses (Open Access)

Among the first white blood cells to respond to bacterial and fungal infections, neutrophils are produced in the bone marrow, released into circulating blood, and recruited to inflamed tissue. The cytokine granulocyte colony-stimulating factor (G��CSF) is used clinically to induce neutrophil mobilization from the marrow. This process was previously demonstrated to require the STAT3 transcription factor (signal transducer and activator of transcription 3), the principal signaling molecule activated upon G-CSF-binding of its receptor, but the mechanism was unknown. The chemokines KC (Cxcl1) and MIP-2 (Cxcl2), and their shared receptor CXCR2 (l8rb), also stimulate neutrophil mobilization, in contrast to SDF-1 (Cxcl12), …

Upregulation Of Reactive Oxygen Species During The Retrovirus Life Cycle And Their Roles In A Mutant Of Moloney Murine Leukemia Virus, Ts1-Mediated Neurodegeneration, Soo Jin Kim

Dissertations and Theses (Open Access)

Viral invasion of the central nervous system (CNS) and development of neurological symptoms is a characteristic of many retroviruses. The mechanism by which retrovirus infection causes neurological dysfunction has yet to be fully elucidated. Given the complexity of the retrovirus-mediated neuropathogenesis, studies using small animal models are extremely valuable. Our laboratory has used a mutant moloney murine leukemia retrovirus, ts1-mediated neurodegneration. We hypothesize that astrocytes play an important role in ts1-induced neurodegeneration since they are retroviral reservoirs and supporting cells for neurons. It has been shown that ts1 is able to infect astrocytes in vivo and in …

Novel Mechanisms Of Antigen Processing That Enhance Bcg Vaccine Efficacy, Christopher R. Singh

Dissertations and Theses (Open Access)

Mycobacterium tuberculosis, the causative agent of tuberculosis, is the most lethal single infectious agent afflicting man today causing 2 million deaths per year. The World Health Organization recommends a vaccine as the best option to prevent this disease. The current vaccine, BCG, has a variable efficacy and does not protect adults. It is known that BCG vaccine becomes sequestered in special phagosome compartments of macrophages that do not fuse with lysosomes. Since lysosome fusion is necessary for peptide production and T cell priming leading to protective T_H1 immunity, we hypothesized that vaccine efficacy is reduced and occurs perhaps …

Role Of Porcine Reproductive And Respiratory Syndrome Virus Non-Structural Protein 1 In Viral Replications And Pathogenesis, Lalit Kumar Beura

School of Veterinary and Biomedical Sciences: Dissertations, Theses, and Student Research

Porcine reproductive and respiratory syndrome virus (PRRSV) is an infectious agent of significant concern to the global swine industry. PRRSV infection of pigs is initiated by a long viremia after which the virus enters in an extended persistent phase of 3-4 months that ultimately is resolved by the immune system. The delayed and weak host adaptive response is responsible for the protracted convalescence period. An initial sub-optimal innate immune response is postulated to be the reason behind such meager adaptive immune response. A major focus of the studies undertaken in this dissertation was to identify the viral non-structural proteins (nsps) …

Glutaredoxin 2 Prevents H2o2-Induced Cell Apoptosis By Protecting Complex I Activity In The Mitochondria, Hongli Wu, Kuiyi Xing, Marjorie F. Lou

School of Veterinary and Biomedical Sciences: Faculty Publications

Glutaredoxin 2 (Grx2) belongs to the oxidoreductase family and is an isozyme of glutaredoxin 1 (Grx1) present in the mitochondria, however its function is not well understood. The purpose of this study is to evaluate the potential anti-apoptotic function of Grx2 by examining its ability to protect complex I in the mitochondrial electron transport system using human lens epithelial cells as a model. We found that cells treated with 200 μM hydrogen peroxide (H2O2) for 24 h exhibited decreased viability and became apoptotic with corresponding Bax up-regulation, Bcl-2 down-regulation, caspase 3 activation and mitochondrial cytochrome c leakage. Grx2 over-expression (OE) …

Regulation Of Cytosolic Phospholipase A2 (Cpla2) And Its Association With Cell Proliferation In Human Lens Epithelial Cells, Yin Wang, Kui-Yi Xing, Marjorie F. Lou

School of Veterinary and Biomedical Sciences: Faculty Publications

PURPOSE. To investigate the molecular mechanism for cytosolic phospholipase A2 (cPLA2) regulation and its association to platelet-derived growth factor (PDGF)-induced cell proliferation.

METHODS. cPLA2 was examined using human lens epithelial (HLE) B3 cells. Reactive oxygen species (ROS) generation induced by PDGF was analyzed by luminescence assay. Cell proliferation was measured by cell counting and by BrdU assay. Human cPLA2 gene was cloned via RT-PCR followed by sitedirected mutagenesis to construct HLE B3 cells expressing either inactive cPLA2 enzyme with S228A mutation (S228A), or cPLA2 truncated at the calcium-binding C2 domain (C2D). Activity of cPLA2 was measured by arachidonic acid (AA) …

Emerging Dynamics Of Human Campylobacteriosis In Southern Ireland, Susan Bullman, Daniel Corcoran, James O'Leary, Derry O'Hare, Brigid Lucey, Roy D. Sleator

Department of Biological Sciences Publications

Infections with Campylobacter spp. pose a significant health burden worldwide. The significance of Campylobacter jejuni/Campylobacter coli infection is well appreciated but the contribution of non-C. jejuni/C. coli spp. to human gastroenteritis is largely unknown. In this study, we employed a two-tiered molecular study on 7194 patient faecal samples received by the Microbiology Department in Cork University Hospital during 2009. The first step, using EntericBio® (Serosep), a multiplex PCR system, detected Campylobacter to the genus level. The second step, utilizing Campylobacter species-specific PCR identified to the species level. A total of 340 samples were confirmed as Campylobacter genus positive, 329 of …

Characterization Of The Serologic Responses To Plasmodium Vivax Dbpii Variants Among Inhabitants Of Pursat Province, Cambodia, Samantha Jones Barnes

USF Tampa Graduate Theses and Dissertations

The Plasmodium vivax Duffy Binding Protein (DBP) is the ligand in the major pathway for P. vivax invasion of human reticulocytes, making it an appealing vaccine candidate. Region II of DBP (DBP-RII) is the minimal portion of the ligand that mediates recognition of the Duffy Antigen Receptor for Chemokines (DARC receptor) on the reticulocyte surface and constitutes the primary vaccine target. Analysis of natural variation in the coding sequences of DBP-RII revealed signature evidence for selective pressure driving variation in the residues of the putative receptor-binding site. We hypothesize that anti-DBP immunity in P. vivax infections is strain-specific and hindered …

Mathematical Modeling And Dynamical Analysis Of The Operation Of The Hypothalamus - Pituitary - Thyroid (Hpt) Axis In Autoimmune (Hashimoto's) Thyroiditis, Balamurugan Pandiyan

Dissertations (1934 -)

This thesis is a mathematical modeling study of the operation of the negative feedback control through the hypothalamus-pituitary- thyroid (HPT) axis in autoimmune (Hashimoto's) thyroiditis. Negative feedback control through the HPT axis is a mechanism in which the high levels of thyroid hormone; free thyroxine (FT4) in the blood inhibits the secretion of the pituitary hormone, thyroid stimulating hormone (TSH) into the blood. Similarly, the low levels of free thyroxine (FT4) sensed by the pituitary gland and then it secretes thyroid stimulating hormone (TSH) into the blood. Autoimmune (Hashimoto's) thyroiditis is a disease in which the immune system turns against …

Caspase-1 Dependent Il-1Β Secretion Is Critical For Host Defense In A Mouse Model Of Chlamydia Pneumoniae Lung Infection, Kenichi Shimada, Timothy R. Crother, Justin Karlin, Shuang Chen, Norika Chiba, V. Krishnan Ramanujan, Laurent Vergnes, David M. Ojcius, Moshe Arditi

All Dugoni School of Dentistry Faculty Articles

Chlamydia pneumoniae (CP) is an important human pathogen that causes atypical pneumonia and is associated with various chronic inflammatory disorders. Caspase-1 is a key component of the ‘inflammasome’, and is required to cleave pro-IL-1β to bioactive IL-1β. Here we demonstrate for the first time a critical requirement for IL-1β in response to CP infection. Caspase-1^−/− mice exhibit delayed cytokine production, defective clearance of pulmonary bacteria and higher mortality in response to CP infection. Alveolar macrophages harbored increased bacterial numbers due to reduced iNOS levels in Caspase-1^−/− mice. Pharmacological blockade of the IL-1 receptor in CP infected wild-type mice …

Immune Evasion Of Porcine Reproductive And Respiratory Syndrome Virus Through Glycan Shielding Involves Both Glycoprotein 5 As Well As Glycoprotein 3, Hiep Vu, Byungjoon Kwon, Kyoung-Jin Yoon, William W. Laegreid, Asit K. Pattnaik, Fernando A. Osorio

School of Veterinary and Biomedical Sciences: Faculty Publications

Passive administration of porcine reproductive and respiratory syndrome virus (PRRSV) neutralizing antibodies (NAbs) can effectively protect pigs against PRRSV infection. However, after PRRSV infection, pigs typically develop a weak and deferred NAb response. One major reason for such a meager NAb response is the phenomenon of glycan shielding involving GP5, a major glycoprotein carrying one major neutralizing epitope. We describe here a type II PRRSV field isolate (PRRSV-01) that is highly susceptible to neutralization and induces an atypically rapid, robust NAb response in vivo. Sequence analysis shows that PRRSV-01 lacks two N-glycosylation sites, normally present in wild-type (wt) PRRSV strains, …

Prevalence Of Myxobolus Cerebralis Infections Among Genetic Lineages Of Tubifex Tubifex At Three Locations In The Madison River, Montana, Nilanjan Lodh, Lori Stevens, Billie Kerans

Clinical Lab Sciences Faculty Research and Publications

Host biodiversity can impact disease risk and influence the transmission of parasitic disease. Stream sediment–dwelling worms, Tubifex tubifex (Clitellata: Oligochaeta), are the definitive host of the parasite Myxobolus cerebralis (Myxozoa: Myxosporea), which causes whirling disease in salmonid fishes. Genetic diversity of T. tubifex is correlated with host susceptibility to M. cerebralis, and mitochondrial Lineage III is generally shown to be more likely to be infected and produce the triactinomyxon (TAM) spores than other lineages. We determined the mitochondrial lineage, relative abundance, and prevalence of infection of T. tubifex collected at 3 sites in the Madison River, Montana, where previous …

Potency Testing For Ntd Vaccines: Determining Relative Potency For The Na-Gst-1 Human Hookworm Vaccine, Amar R. Jariwala, Brian Keegan, Pavithra Raghavendra, Jordan L. Plieskatt, Maria Elena Bottazzi, Peter J. Hotez, Jeffrey M. Bethony

Microbiology, Immunology, and Tropical Medicine Posters and Presentations

Over the next decade, a new generation of vaccines will target the neglected tropical diseases (NTDs) . The goal of most NTD vaccines will be to reduce the morbidity and decrease the chronic debilitating nature of these often-forgotten infections - outcomes that are hard to measure in the traditional potency-testing paradigm . The absence of measurable correlates of protection, a lack of permissive animal models for lethal infection, and a lack of clinical indications that do not include the induction of sterilizing immunity required us to reconsider the traditional bioassay methods for determining vaccine potency . Owing to these limitations, …

Hypervirulent Chlamydia Trachomatis Clinical Strain Is A Recombinant Between Lymphogranuloma Venereum (L(2)) And D Lineages, Naraporn Somboonna, Raymond Wan, David M. Ojcius, Matthew A. Pettengill, Sandeep J. Joseph, Alexander Chang, Ray Hsu, Timothy D. Read, Deborah Dean

All Dugoni School of Dentistry Faculty Articles

Chlamydia trachomatis is an obligate intracellular bacterium that causes a diversity of severe and debilitating diseases worldwide. Sporadic and ongoing outbreaks of lymphogranuloma venereum (LGV) strains among men who have sex with men (MSM) support the need for research on virulence factors associated with these organisms. Previous analyses have been limited to single genes or genomes of laboratory-adapted reference strain L₂/434 and outbreak strain L₂b/UCH-1/proctitis. We characterized an unusual LGV strain, termed L₂c, isolated from an MSM with severe hemorrhagic proctitis. L₂c developed nonfusing, grape-like inclusions and a cytotoxic phenotype in culture, …

Analysis And Interpretation Of Factors Leading To Increased Aids Prevalence In Sub-Saharan Africa, William Kalhorn

Department of Environmental Studies: Undergraduate Student Theses

My thesis research project focuses on the major factors that are contributing to the worst disease epidemic on the planet today. I have aimed to determine what may be some of the most important factors contributing to highly variable difference in HIV/AIDS prevalence rates are among the regions of East, West, and South Africa.  The HIV/AIDS epidemic has been growing and expanding to new areas of the world since the first case arose in 1959 in what is now called Kinshasa, Congo (Avert, 2011). The AIDS/HIV epidemic is believed to have originated on the African continent, and this is where …

Archaeoparasitology Of Chaco Canyon, Rachel Paseka

Department of Environmental Studies: Undergraduate Student Theses

Ancient cultures of the Colorado Plateau have been a focus of archaeoparasitology since its inception, and a vast parasitological history is recorded in coprolites preserved in this arid region. The inhabitants of Chaco Canyon dominated Ancestral Puebloan culture between 1050 and 1120 AD and were responsible for the construction of great towns, road systems, and early agriculture. Analysis of the parasites preserved in fecal remains contributes to an increased knowledge of ancient Chacoan health and culture. Nineteen coprolites from four sites in Chaco Canyon were rehydrated and analyzed microscopically for parasite remains. Rhabditiform and filariform nematode larvae were found from …

Heartworm In Canines: Trends In Rhode Island Shelter Populations, Kelsey L. Mckenna

Senior Honors Projects

Heartworm in Canines

Kelsey McKenna

Faculty Sponsor: Darlene Jones, DVM, Animal Science

Each year thousands of dogs in the United States become infected with heartworm, which is caused by Dirofilaria immitis. D. immitis is a parasite that is transmitted to dogs via a bite by an infected mosquito. Nine of the seventy competent mosquito species reside in Rhode Island. The true incidence of D. immitis is unknown. Current incidence maps are derived from data generated at veterinary clinics and do not include shelter dogs. The objective of this study is twofold: to determine the prevalence of D. immitis in …

Role Of Vitamin-D3 And Retinoic Acid In A Human Thp-1 Macrophage Model Of Mycobacterium Tuberculosis Infection, Jaymie L. Estrella

Dissertations and Theses (Open Access)

Mycobacterium tuberculosis (Mtb) replicates within the human macrophages and we investigated the activating effects of retinoic acid (RA) and vitamin D3 (VD) on macrophages in relation to the viability of Mtb. A combination of these vitamins (RAVD) enhanced the receptors on THP-1 macrophage (Mannose receptor and DC-SIGN) that increased mycobacterial uptake but inhibited the
subsequent intracellular growth of Mtb by inducing reactive oxygen species (ROS) and autophagy. RAVD also enhanced antigen presenting and homing receptors in THPs that suggested an activated phenotype for THPs following RAVD treatment. RAVD mediated activation was also associated with a marked phenotypic change in Mtb …

Immune Modulation Of The Mycobacterium Tuberculosis Granulomatous Response, Kerry J. Welsh

Dissertations and Theses (Open Access)

Tuberculosis (TB) remains a major public health burden. The immunocompetant host responds to Mycobacterium tuberculosis (MTB) infection by the formation of granulomas, which initially prevent uncontrolled bacterial proliferation and dissemination. However, increasing evidence suggests that granuloma formation promotes persistence of the organism by physically separating infected cells from effector lymphocytes and by inducing a state of non-replicating persistence in the bacilli, making them resistant to the action of antibiotics. Additionally, immune-mediated tissue destruction likely facilitates disease transmission. The granulomatous response is in part due to mycobacterial glycolipid antigens. Therefore, studies were first undertaken to determine the innate mechanisms of mycobacterial …

Molecular Mechanisms Underlying The Transcriptional Regulation Of T Helper 17 And Regulatory T Cells, Gustavo Javier Martinez

Dissertations and Theses (Open Access)

CD4⁺ T helper (Th) lymphocytes are vital for integrating immune responses by orchestrating the function of other immune cell types. Naïve Th cells can differentiate into different effector subsets that are characterized by their cytokine profile and immune regulatory functions. These subsets include Th1, Th2, Th17, natural and inducible regulatory T cells (nTreg and iTreg respectively), among others. We focused our investigation on two Th lineages, Th17 and regulatory T cells, with opposing functions in the immune system. These subsets have been suggested to be reciprocally regulated since they both require TGF-b for their development. We investigated the role …

Host And Distribution Lists Of Chiggers (Trombiculidae And Leeuwenhoekiidae), Of North American Wild Vertebrates North Of Mexico, Brianne L. Walters, John O. Whitaker Jr., Nicholas S. Gikas, William J. Wrenn

Harold W. Manter Laboratory of Parasitology: Faculty Publications

Information concerning chiggers found on wild vertebrates of North America north of Mexico is summarized. Included are lists a) of the chiggers organized taxonomically, b) hosts from which each species has been reported, and c) states and provinces with references for each separate record

Rickettsia Parkeri In Gulf Coast Ticks, Southeastern Virginia, Usa, Chelsea L. Wright, Robyn M. Nadolny, Ju Jiang, Allen L. Richards, Daniel E. Sonenshine, Holly D. Gaff, Wayne L. Hynes

Biological Sciences Faculty Publications

We report evidence that Amblyomma maculatum tick populations are well established in southeastern Virginia. We found that 43.1% of the adult Gulf Coast ticks collected in the summer of 2010 carried Rickettsia parkeri, suggesting that persons living in or visiting southeastern Virginia are at risk for infection with this pathogen.

Tumor Recognition And Self-Recognition Induce Distinct Transcriptional Profiles In Antigen-Specific Cd4 T Cells, Adam J. Adler

UCHC Articles - Research

Tumors express a wide variety of both mutated and nonmutated Ags. Whether these tumor Ags are broadly recognized as self or foreign by the immune system is currently unclear. Using an autochthonous prostate cancer model in which hemagglutinin (HA) is specifically expressed in the tumor (ProHA × TRAMP mice), as well as an analogous model wherein HA is expressed in normal tissues as a model self-Ag (C3HA^high), we examined the transcriptional profile of CD4 T cells undergoing Ag-specific division. Consistent with our previous data, transfer of Ag-specific CD4 T cells into C3HA^high resulted in a functionally inactivated …

The Release Of Calcium In Bacillus Anthracis Pathogenicity Methods, Natiera Magnuson, Manomita Patra Bhowmik, Maria Elena Reynaga, Ernesto Abel-Santos

Festival of Communities: UG Symposium (Posters)

Anthrax infection starts with germination of Bacillus anthracis spores in macrophages. Some bacteria, including B. anthracis, can sporulate in response to environmental stress, such as starvation. During germination, large concentrations of calcium ions are released from the B. anthracis spore. Calcium ions are hydrophilic secondary messengers, and may therefore interfere with detection of the spore by confusing the cell signaling pathways. We investigated calcium release on infected macrophage viability by replacing the calcium stored in B. anthracis spores for other cations via demineralization/remineralization. It was discovered that calcium ions typically out-performed other cations in germination of B. anthracis.

Molecular Structures Of Prrsv That Contribute To Prrsv Protective Immunity, Asit K. Pattnaik

School of Veterinary and Biomedical Sciences: Faculty Publications

One of the objectives of the proposal is to delineate the regions of the two glycoproteins (GP2 and GP4) of PRRSV that interact with CD163. Other objectives of the proposal are to generate antibodies to these small regions of the glycoproteins as well as to the full-length proteins for future studies to determine if any of these antibodies possess PRRSV neutralizing activity.

To carry out the studies in the proposed objectives, we generated a series of mutants of GP2 as well as GP4 proteins in which various regions were specifically removed by manipulating the plasmids encoding these proteins. We then …

Estrogenic Regulation Of The Immune System In A Murine Model For Systemic Lupus Erythematosus, Matthew James Zuber

Biology Honors Papers

Systemic Lupus Erythematosus is a damaging autoimmune disease afflicting millions of people worldwide. Lupus is characterized by an overabundance of autoantibodies, proteins directing the immune system to destroy a person's own body, what it would normally be protecting. The molecular mechanisms, environmental influences, and genetic predispositions of Lupus are not yet fully understood. However, nine out of ten Lupus patients are women between the age of puberty and menopause, when estrogen levels are highest. The fact that women are significantly more prone to suffer from Lupus than men leads experts to believe that the sex hormone estrogen which is present …