Immunology and Infectious Disease Commons^™

Regulations Of Pathogenic Cd4+ T Helper Lymphocytes In Inflammatory Diseases, Handong Zheng

Biomedical Sciences ETDs

In this comprehensive project, three interrelated studies with distinct foci were employed to understand the regulations of specific CD4⁺ T helper cell population in inflammatory diseases.

Pathogenic TH17 cells play an essential role in the initiation and development of both human multiple sclerosis (MS) and animal experimental autoimmune encephalomyelitis (EAE). Nevertheless, the underlying mechanism by which the pathogenicity of TH17 cells is controlled in the autoimmune neuro-inflammation remains unclear. In aim 1, we revealed that lumican (Lum), an extracellular matrix (ECM) protein, negatively regulates encephalitic TH17 cell responses. Our findings highlighted a TH17 cell-intrinsic effect of Lum in suppressing …

Role Of Neutrophils In The Modulation Of Host Responses To Human Respiratory Pneumovirus Infection, Nagarjuna Reddy Cheemarla

LSU Doctoral Dissertations

Neutrophils are the most abundant leukocytes (50% to 70%) in humans and are the first immune cell population recruited to the sites of infection. They are known to act as the first line of innate immune defense against invading pathogens, and more recently, to playing a crucial role in orchestrating adaptive immune responses. The role of neutrophils in the respiratory viral infections till date remains unclear and controversial. Previous studies demonstrated both beneficial as well as pathogenic role for neutrophils in respiratory viral infections, especially influenza.

Previous findings reported an early and high influx of neutrophils into the airways early …

Inflammation And Immune Evasion Coexist In Treponema Pallidum-Infected Skin, Rodolfo Trujillo, Jorge Cervantes, Kelly L. Hawley, Adriana R. Cruz, Sankhiros Babapoor, Michael Murphy, Soheil S. Dadras, Juan C. Salazar

Biology Faculty Publications

Syphilis is a systemic, multistage, sexually transmitted infection caused by the highly invasive spirochetal bacterium, Treponema pallidum, subspecies pallidum. In the United States, the annual rate of primary and secondary syphilis (SS) between 2002 and 2016 has increased from 2.1 to 8.7 cases per 100,000.¹ Gestational and congenital syphilis cases have also increased in the last few years. There is no evidence of a change in T pallidum susceptibility to penicillin as an explanation for the significant increase in the number of syphilis cases in the United States. It is more likely that changes in risk-taking behavior in …

Quantifying Effects Of Neutrophil Memory On Migration Patterns Using Microfluidic Platforms And Ode Modeling Of The Mechanistic Molecular Pathways, Brittany P. Boribong, Mark J. Lenzi, Mirjam Sarah Kadelka, Stanca Ciupe, Liwu Li, Caroline N. Jonea

Biology and Medicine Through Mathematics Conference

No abstract provided.

The Role Of Outcome Preferences In Optimizing Heterogenous Disease Control Strategies., Evan Milliken

Biology and Medicine Through Mathematics Conference

No abstract provided.

First Results On Survival From A Large Phase 3 Clinical Trial Of An Autologous Dendritic Cell Vaccine In Newly Diagnosed Glioblastoma, Linda M. Liau, Keyoumars Ashkan, David D. Tran, Jian L. Campian, John E. Trusheim, Charles S. Cobbs, Jason A. Heth, Michael Salacz, Sarah Taylor, Stacy D. D'Andre, Fabio M. Iwamoto, Edward J. Dropcho, Yaron A. Moshel, Kevin A. Walter, Clement P. Pillainayagam, Robert Aiken, Rekha Chaudhary, Samuel A. Goldlust, Daniela A Bota, Paul Duic, Jai Grewal, Heinrich Elinzano, Steven A. Toms, Kevin O. Lillehei, Tom Mikkelsen, Tobias Walbert, Steven R. Abram, Andrew J. Brenner, Steven Brem, Matthew G. Ewend, John L. Villano

Internal Medicine Faculty Publications

Background: Standard therapy for glioblastoma includes surgery, radiotherapy, and temozolomide. This Phase 3 trial evaluates the addition of an autologous tumor lysate-pulsed dendritic cell vaccine (DCVax^®-L) to standard therapy for newly diagnosed glioblastoma.

Methods: After surgery and chemoradiotherapy, patients were randomized (2:1) to receive temozolomide plus DCVax-L (n = 232) or temozolomide and placebo (n = 99). Following recurrence, all patients were allowed to receive DCVax-L, without unblinding. The primary endpoint was progression free survival (PFS); the secondary endpoint was overall survival (OS).

Results: For the intent-to-treat (ITT) population (n = 331), median OS (mOS) was 23.1 months …

In Vivo And In Vitro Studies Of Cry5b And Nicotinic Acetylcholine Receptor Agonist Anthelmintics Reveal A Powerful And Unique Combination Therapy Against Intestinal Nematode Parasites, Yan Hu, Melanie Miller, Bo Zhang, Thanh-Thanh Nguyen, Martin K. Nielsen, Raffi V. Aroian

Veterinary Science Faculty Publications

Background

The soil-transmitted nematodes (STNs) or helminths (hookworms, whipworms, large roundworms) infect the intestines of ~1.5 billion of the poorest peoples and are leading causes of morbidity worldwide. Only one class of anthelmintic or anti-nematode drugs, the benzimidazoles, is currently used in mass drug administrations, which is a dangerous situation. New anti-nematode drugs are urgently needed. Bacillus thuringiensis crystal protein Cry5B is a powerful, promising new candidate. Drug combinations, when properly made, are ideal for treating infectious diseases. Although there are some clinical trials using drug combinations against STNs, little quantitative and systemic work has been performed to define the …

Schistosomiasis In The Wild: A Transcriptomics Perspective On Field-Derived Biomphalaria Pfeifferi And Schistosoma Mansoni, And Their Interactions, Sarah K. Buddenborg

Biology ETDs

Schistosomiasis, caused by trematodes in the genus Schistosoma, is a widespread neglected tropical disease with the species S. mansoni infecting over 100 million people. We aimed to better understand the snail host and parasite responses during intramolluscan stages of infection by performing dual RNA-Seq on field-collected snails with natural infections from western Kenya. We collected uninfected Biomphalaria pfeifferi, B. pfeifferi with a patent cercariae-producing S. mansoni infection, and B. pfeifferi exposed to field-collected S. mansoni at 1 and 3d (days post infection).

We first created a high-quality B. pfeifferi transcriptome to identify the snail response to S. mansoni infection. …

Serum Lipidomics Of Bovine Paratuberculosis: Disruption Of Choline-Containing Glycerophospholipids And Sphingolipids, Paul L. Wood, Erdal Erol, Glen F. Hoffsis, Margaret Steinman, Jeroen Debuck

Veterinary Science Faculty Publications

Objectives: Bovine paratuberculosis is a devastating infection with Mycobacterium avium subspecies paratuberculosis that ultimately results in death from malnutrition. While the infection is characterized by a long (2–4 years) subclinical phase with immune activation, ultimately host defense mechanisms fail and the bacteria spread from the small intestine to other organs. Since both the gastrointestinal tract and liver are essential for the biosynthesis of structural glycerophospholipids, we investigated the circulating levels of these lipids in field infections and experimentally infected cattle.

Methods: Serum lipidomics of control and M. avium subspecies paratuberculosis–infected cattle were performed utilizing high-resolution mass spectrometry.

Results: In …

Evolution Of Bordetella Pertussis Genome May Play A Role In The Increased Rate Of Whooping Cough Cases In The United States, Kevin Loftus

Senior Honors Projects, 2010-2019

Bordetella pertussis is the bacterium responsible for pertussis, a disease commonly referred to as whooping cough. Recently, pertussis has made a resurgence in the U.S. despite high-vaccination coverage. Possible causes of the increased number of pertussis cases include genetic evolution of B. pertussis, increased awareness of the disease, better laboratory diagnostics, and the switch from a whole-cellular (wP) vaccine to an acellular vaccine (aP) in the 1990s. Fortunately, just as B. pertussis is evolving, so is the arsenal of technologies used to understand and combat this pathogenic bacterium. Whole genome sequencing is one technology that helps researchers better understand …

Elucidation Of The Functions Of Neuropilin 2 In Osteoclasts In Promoting Prostate Cancer Bone Metastasis., Navatha S. Polavaram

Theses & Dissertations

Bone metastasis is one of the major clinical concerns that causes skeletal related malignancies and increased mortality. Bone is one of the preferred sites for metastatic prostate cancer. The metastatic prostate cancer cells interact with bone cells (osteoblasts and osteoclasts) resulting in an imbalance in the bone homeostasis leading to increased activation of osteoblasts over osteoclasts. Our preliminary data indicated a non-tyrosine kinase receptor Neuropilin 2 (NRP2) is expressed in osteoclasts induced by metastatic prostate cancer cells and acts as a negative regulator of osteoclast differentiation and function. We hypothesize that prostate cancer -induced NRP2 expression in osteoclasts is necessary …

Potential Vectors Of Dog Heartworm, Dirofilaria Immitis, In Arkansas And Seasonal Transmission In The United States, Sofija Todorovic

Student Theses and Dissertations

Dirofilaria immitis (Leidy), is a mosquito-borne, parasitic filarid responsible for heartworm disease in vertebrates. A mosquito survey, focusing on diurnal species, was conducted from May to December 2016 to identify the prevalence of D. immitis in mosquitoes collected at residential entryways in Jonesboro, AR. Aedes albopictus (Skuse), a diurnal mosquito, was collected in low abundance (3.4%) with 16.7% mosquitoes positive for heartworm microfilariae. Dirofilaria immitis was observed in 11.2% of the total mosquitoes collected. The second study estimated the seasonality of heartworm disease in four high-risk US cities. Daily average and hourly temperatures were used to predict the presence of …

Preliminary Work On Infestation Dynamics And Stable Isotope Ecology Of A Coral Reef Micropredator, William Garrett Jenkins

Student Theses and Dissertations

Despite the significant ecological role that parasites likely play within their respective communities, little is understood about the role that they play within food webs. The studies presented herein sought to expand upon the understanding of the role that gnathiid isopods, a marine fish ectoparasite, play within coral reef ecological communities by: a) assessing the effect of host physical condition on susceptibility to exploitation by a gnathiid isopod and b) by conducting a comprehensive, preliminary, study on the stable isotope ecology of these micropredators. Host fish which were experimentally injured during field trials exhibited a higher probability of being parasitized …

The Small Rna Complement Of Adult Schistosoma Haematobium., Andreas J Stroehlein, Neil D Young, Pasi K Korhonen, Ross S Hall, Aaron R Jex, Bonnie L Webster, David Rollinson, Paul J Brindley, Robin B Gasser

Microbiology, Immunology, and Tropical Medicine Faculty Publications

BACKGROUND: Blood flukes of the genus Schistosoma cause schistosomiasis-a neglected tropical disease (NTD) that affects more than 200 million people worldwide. Studies of schistosome genomes have improved our understanding of the molecular biology of flatworms, but most of them have focused largely on protein-coding genes. Small non-coding RNAs (sncRNAs) have been explored in selected schistosome species and are suggested to play essential roles in the post-transcriptional regulation of genes, and in modulating flatworm-host interactions. However, genome-wide small RNA data are currently lacking for key schistosomes including Schistosoma haematobium-the causative agent of urogenital schistosomiasis of humans.

METHODOLOGY: MicroRNAs (miRNAs) and other …

A Time Course Study Of Rotavirus-Infected Intestinal Cells Treated With Stilbenoids And The Regulation Of Apoptosis, Rebecca D. Parr, Caleb M. Witcher, Rebekah Napier-Jameson, Hannah L. Wilson, Stormey Wisdom, Macie N. Mattila, Essence B. Strange, Josephine Taylor, Beatrice Clack, Fabricio Medina-Bolivar, Judith M. Ball

Faculty Publications

This is a time course study of virus –host interactions that are modified with the addition of two small natural products. They appear to effect virus replication and the host response to the infection.

Enhanced Production Of Pro-Il-1Βeta Contributes To Immunopathology During The Coinfection Of Influenza A Virus And Streptococcus Pneumoniae, Angeline E. Rodriguez

Graduate Theses/Dissertations

Viral bacterial coinfections are known to cause severe pneumonia, especially in the elderly and in pediatric patients. Antibiotics like β-Lactams kill the bacteria but fail to improve symptoms suggesting a faulty immune system may play an important role in the disease. Interleukin-1β (IL-1β) is an important immune signaling cytokine responsible for inflammation. It exists as an inactive precursor that can be activated by caspase-1 containing inflammasomes (multi-protein complex). Influenza A virus (IAV) and Streptococcus pneumoniae (S. pneumoniae) activate the inflammasome through the NOD-like receptor protein NLRP3 and/or AIM2. Previous reports in mice indicate that IL-1β levels are dramatically …

Investigation Of Bradyzoite Differentiation Initiation In Toxoplasma Gondii, Harim I. Won, Paul H. Davis Ph.D.

Theses/Capstones/Creative Projects

Like other eukaryotic organisms, Toxoplasma gondii promoters feature both constitutive and life-stage regulated cis-elements. Using a transcriptomic microarray approach, a cluster of transcripts upregulated early during bradyzoite differentiation was identified. Computational analysis of the promoter regions of these “up-early” transcripts identified a shared upstream consensus motif, a putative transcription factor binding site. Using a dual luciferase assay adapted for recombinational cloning and reporter gene quantification by qPCR, we demonstrate developmental stage-specific expression of the luciferase reporter gene inserted downstream of the transcription factor binding site. The shared consensus motif was found to be an autonomous cis-element by conversion …

Cddo-Me Attenuates Inflammation In Healthy And Systemic Sclerosis Macrophages, Saemi Han, Rajan Bhandari, Patricia A. Pioli

Wetterhahn Science Symposium Posters 2018

No abstract provided.

Group B Streptococcus Exploits Vaginal Epithelial Exfoliation For Ascending Infection, Jay Vornhagen, Blair Armistead, Verónica Santana-Ufret, Claire Gendrin, Erica Boldenow

University Faculty Publications and Creative Works

Thirteen percent of pregnancies result in preterm birth or stillbirth, accounting for fifteen million preterm births and three and a half million deaths annually. A significant cause of these adverse pregnancy outcomes is in utero infection by vaginal microorganisms. To establish an in utero infection, vaginal microbes enter the uterus by ascending infection; however, the mechanisms by which this occurs are unknown. Using both in vitro and murine models of vaginal colonization and ascending infection, we demonstrate how a vaginal microbe, group B streptococcus (GBS), which is frequently associated with adverse pregnancy outcomes, uses vaginal exfoliation for ascending infection. GBS …

Changes In The Microbial Community Of Lubomirskia Baicalensis Affected By Red Sponge Disease, Colin Rorex

Electronic Theses and Dissertations

Lake Baikal is the oldest known lake and a unique ecosystem, home to several species of fresh water sponge. A disease outbreak affecting the dominant species, Lubormirskia baialensis, was recently reported. The cause of the disease has not been determined but one of the current hypothesis is that the increase in methane concentration is correlated to the disease outbreak. This pilot study characterized the microbiomes of sick and healthy sponges through the use of 16S rRNA sequencing. Sick sponge microbiomes shared a conserved group of taxa while the healthy sponge microbiomes had greater diversity. Indicator species analysis identified two significant …

Concepts In Animal Parasitology: Permission To Publish Agreement, University Of Nebraska-Lincoln Libraries

Concepts in Animal Parasitology

Blank Permission to Publish agreement form for authors of the Concepts in Animal Parasitology textbook/open educational resource.

Tumor Immunotherapy: Mechanisms Of Acquired Resistance And Characterization Of Immune Related To Xicities, Ashvin Jaiswal

Dissertations and Theses (Open Access)

Tumor immunotherapy has shown very promising clinical benefit across an array of cancers; however, two major challenges remain unresolved in the field. First, many patients do not respond to therapy at all or relapse after a period of remission. Second, there are often dose-limiting immune related adverse effects associated with immunomodulation.

In order to understand the mechanisms employed by tumors to evade immunotherapeutic responses, we established a murine model of melanoma designed to elucidate the molecular mechanisms underlying immunotherapy resistance. Through multiple in vivo passages, we selected a B16 melanoma tumor line that evolved complete resistance to combination blockade of …

Evidence For Organelle-Like Extracellular Vesicles From A Parasite Of Drosophila And Their Function In Suppressing Host Immunity, Mary Heavner

Dissertations, Theses, and Capstone Projects

Parasitic wasps act as keystone species in natural ecosystems. Adept at suppressing immunity of their insect hosts, these natural enemies of insect pests are used for biocontrol in many parts of the world. Female parasitic wasps of the closely-related species Leptopilina heterotoma (Lh), a generalist of many Drosophilia flies, and Leptopilina boulardi (Lb), a specialist on flies of the melanogaster subgroup, produce venom and virus-like particles (VLPs) in their long gland-reservoir complexes, a secretory organ connected to ovipositors. Venom and VLPs are deposited, along with wasp eggs, into the body of the wasp’s larval fly host …

Herpes Zoster Patient Education: A Coloring Book Approach, Sophia Charuhas

Senior Honors Theses

Shingles, the disease caused by the herpes zoster virus, is a widespread and widely misunderstood illness in the United States. It is preventable, but many at-risk patients do not know what measures they may take to prevent it. Clear communication from physician to patient is crucial for patient understanding of diseases. Many patient education materials on herpes zoster currently available are often unused. It is therefore beneficial to public health to disseminate new mediums of medical communication, and one way of accomplishing this is through adult coloring books. The pathophysiology of herpes zoster virus is here explored and the idea …

Investigation Into The Causes And Severity Of The 1918 Influenza Pandemic, Alex T. Freedenberg

The Review: A Journal of Undergraduate Student Research

The 1918 Influenza outbreak is regarded as one of the worst pandemics in human history due to its widespread effects across the globe and its high death rate. This death rate was unusual among influenza infections as most strains do not cause the amount of death that is seen in this outbreak, with 20 million dead as a conservative estimate and 100 million by other estimations. This pandemic was not very well contained for a plethora of reasons. Two main reasons are that it came at a time when understanding viral mechanics still escaped medical professionals, and due to the …

Genotype-Specific Insertion Of Cytotoxic Genetic Elements Into Cancer Cells, Ryan Englander

University Scholar Projects

The new gene editing system CRISPR/Cas9, composed of a complex composed of a guide RNA and the Cas9 endonuclease, promises to revolutionize biological research and potentially allow clinicians to directly modify patient DNA in vivo. While its applications in the treatment of genetic diseases and in modifying immune cells for immunotherapy are currently being explored, CRISPR/Cas9’s potential utility as a modular system for targeting tumor-specific mutated sequences has not as of yet been explored. While CRISPR/Cas9 is specific enough to target small insertions and deletions or gross chromosomal rearrangements, it is not specific enough to reliably restrict editing to …

Autoimmune Disorders And Hypersensitivities In The Developed World, Margaret S. Bohm

Conspectus Borealis

No abstract provided.

The Polyphyly Of Plasmodium: Comprehensive Phylogenetic Analyses Of The Malaria Parasites (Order Haemosporida) Reveal Widespread Taxonomic Conflict, Spencer C. Galen, Janus Borner, Ellen S. Martinsen, Juliane Schaer, Christopher C. Austin, Christopher J. West, Susan L. Perkins

Harold W. Manter Laboratory of Parasitology: Library Materials

The evolutionary relationships among the apicomplexan blood pathogens known as the malaria parasites (order Haemosporida), some of which infect nearly 200 million humans each year, has remained a vexing phylogenetic problem due to limitations in taxon sampling, character sampling and the extreme nucleotide base composition biases that are characteristic of this clade. Previous phylogenetic work on the malaria parasites has often lacked sufficient representation of the broad taxonomic diversity within the Haemosporida or the multi-locus sequence data needed to resolve deep evolutionary relationships, rendering our understanding of haemosporidian lifehistory evolution and the origin of the human malaria parasites incomplete. Here …

Out Of The Shell: Exploring The Phagocytic Capabilities Of The B Cell And Isolated Lymphoid Follicle-Lie Structures In The Red-Eared Slider, Trachemys Scripta, Marc A. Ashford Jr.

Theses and Dissertations

Management of immunity is crucial for survival in all living organisms. While there is a large amount of research for established model organisms, such as the mouse model, much less is known about reptiles. When compared to immunity in mammals, we discover many differences such as susceptibility to certain pathogens, alteration of immune processes due to environmental temperature, the total absence of certain lymphoid organs contained in mammals, among many others. Despite this, the reptile has shown in many studies that they are worthy systems to study immunity in an evolutionary perspective and recent studies may show that they may …

Surveillance On The Endemic Of Zika Virus Infection By Meteorological Factors In Colombia: A Population-Based Spatial And Temporal Study, Lung-Chang Chien, Ro-Ting Lin, Yunqi Liao, Francisco S. Sy, Adriana Pérez

School of Public Health Faculty Research

Background Zika virus (ZIKV) infection is a pandemic and a public health emergency. It is transmitted by mosquitoes, primarily the Aedes genus. In light of no treatment currently, it is crucial to develop effective vector control programs to prevent the spread of ZIKV infection earlier when observing possible risk factors, such as weather conditions enhancing mosquito breeding and surviving. Methods This study collected daily meteorological measurements and weekly ZIKV infectious cases among 32 departments of Colombia from January 2015–December 2016. This study applied the distributed lag nonlinear model to estimate the association between the number of ZIKA virus infection and …