Immunology of Infectious Disease Commons^™

The Role Of Tumor Microenvironment In Glioblastoma Multiforme(Gbm) Therapeutic Resistance, Kwesi E. Taylor

Master's Theses or Doctor of Nursing Practice

Despite significant advances in cancer research and treatment, Glioblastoma multiforme (GBM) remains one of the most difficult cancers to treat effectively, with minimal improvement in long-term survival rates over the past few decades. This is largely attributed to tumor heterogeneity and the ability of tumor cells to develop adaptive resistance mechanisms supported by the tumor microenvironment (TME). Although the TME is recognized as a key contributor to tumor progression and therapeutic resistance, the underlying molecular pathways and regulatory genes remain incompletely understood. This study investigated the role of the tumor microenvironment in GBM therapeutic resistance using a bioinformatics approach. Single-cell …

Nanoparticle Carriers Enhance The Prophylactic Antiviral Effects Of Dsrna In Vitro And Ex Vivo, Shayne Oberhoffner, Stephanie Dewitte-Orr, Starla Richardson, Leah Haile, Dominique Daniels, Erin Cooper, Aizah Ijaz, Janet Velasquez Perez, Mathilde Peruzzi, Bertrand Collet, Paul Craig, Kristof Jenik

Theses and Dissertations (Comprehensive)

Aquaculture now outpaces traditional capture fisheries as the world population and demand for sustainable protein sources increases. Wild and farmed species are increasingly susceptible to pathogen spread as global temperatures rise and stocking densities increase. Despite the devastating losses experienced by aquaculture due to viral infections, there remain few effective prophylactic antiviral therapeutics. Long double-stranded (ds)RNA is a uniquely viral molecule produced by nearly all viruses during their replication cycle, and its detection by salmonids like rainbow trout (Oncorhynchus mykiss) and chinook salmon (Oncorhynchus tshawytsha) leads to the establishment of a defensive antiviral state. Previous in vitro studies demonstrated a …

Adiponectin-Regulated Macrophage Responses In Aspergillus Fumigatus Infection: Mechanisms Of Uptake And Killing, Sri Harshini Goli

All-Inclusive List of Electronic Theses and Dissertations

Invasive aspergillosis (IA), caused by Aspergillus fumigatus, is a life-threatening infection in immunocompromised individuals, necessitating novel host-directed therapies. Macrophages are pivotal in antifungal defense, yet their function can be dysregulated; the influence of the adipokine adiponectin (APN) on this process is not fully understood. This thesis investigated the role of APN signaling in alveolar macrophage (AM) and bone marrow-derived macrophage (BMDM) responses to A. fumigatus and assessed the therapeutic potential of the APN receptor agonist, AdipoRon. Initial studies revealed that genetic deficiency in APN or its receptors renders AMs intrinsically pro-inflammatory and significantly impaired fungicidal activity against A. fumigatus. Subsequent …

Which Costimulatory Domains In Chimeric Antigen Receptor T Cells Induce Cytokine Responses That Are Linked To A More Toxic Car T Cell Therapy In Acute Lymphocytic Leukemia?, Elisabeth Cohen

Longwood Senior Thesis Proposal

No abstract provided.

Impact Of Temperature And Microbial Infection On The Honey Bee Hemocytes, Michael E. Oeth

Master's Theses

Introduction

Honey bees (Apis mellifera) rely on hemocytes for immunity, wound healing, and hemolymph homeostasis. While 32°C reflects optimal hive conditions, suboptimal temperatures (22°C) and stressors like pathogens (Varroa destructor, bacteria) or pesticides impair hemocyte function. Using clodronate liposomes (CLD) to deplete hemocytes, we assessed how immune suppression interacts with these stressors.

Methods

Newly emerged (5-day-old) and older (15-day-old) bees were assigned to: CLD, control liposomes (LP), PBS, injection wound, or no treatment. Cohorts were exposed to 32°C (optimal) or 22°C (stressful for non-immunosuppressed bees). Fifteen-day-old bees were challenged with Escherichia coli or Staphylococcus aureus. Survival, hemolymph volume, and hemocyte …

Comprehensive Sumo Proteomic Analyses Identify Hiv Latency-Associated Proteins In Microglia., Fergan Imbert, Dianne Langford

Rowan-Virtua School of Osteopathic Medicine Departmental Research

SUMOylation, the post-translational modification of proteins by small ubiquitin-like modifiers, plays a critical role in regulating various cellular processes, including innate immunity. This modification is essential for modulating immune responses and influencing signaling pathways that govern the activation and function of immune cells. Recent studies suggest that SUMOylation also contributes to the pathophysiology of central nervous system (CNS) viral infections, where it contributes to the host response and viral replication dynamics. Here, we explore the multifaceted role of SUMOylation in innate immune signaling and its implications for viral infections within the CNS. Notably, we present novel proteomic analyses aimed at …

Functional Analysis Of Ligand Binding Domain 2 Of Outer Surface Protein C Of Borreliella Burgdorferi, Gavin Z. Chambers

Theses and Dissertations

Lyme disease, caused by the spirochete Borreliella burgdorferi, is the most common vector-borne infection in North America. A critical determinant of early mammalian infection is outer surface protein C (OspC), a highly variable lipoprotein that is indispensable for spirochete survival but whose precise function remains unresolved. OspC has been proposed to mediate diverse roles, including complement evasion, adhesion, tissue dissemination, and antiphagocytic activity, supporting the view that it is a multifunctional virulence factor. Structural studies have identified two putative ligand-binding domains (LBD1 and LBD2), with LBD2 forming a solvent-exposed crown at the membrane-distal end of the OspC dimer.

To …

The Role Of Host Factor Sptbn1 In Hiv-1 Capsid Uncoating In Human Microglial Cells, Callie Marie Fry

Graduate Theses/Dissertations

HIV-1 is the virus that causes acquired immunodeficiency syndrome (AIDS), and currently, there is no cure once an individual is infected. The development of new drugs targeting HIV-1 replication steps is essential for keeping viral loads low or undetectable to prevent further transmission. An attractive replication step for new drug targets is viral capsid uncoating, where the virus loses the protein structure encapsulating the genome. The exact mechanism of capsid uncoating is unknown; however, several host-factors may be involved including protein SPTBN1. Recent studies have shown a significant decrease in viral infectivity when SPTBN1 is knocked down, yet its role …

Lack Of Inflammatory Response In Mouse Embryonic Cells To Listeria Infection, Damilola Oyebode

Master's Theses

Approximately 1 in 5 pregnancies in the United States results in miscarriage, with a significant percentage of these losses attributed to failed implantation due to immunological challenges encountered by the early embryo. Recent research has shown that key cell types within mouse blastocysts, including embryonic stem cells (ESCs) and trophoblast stem cells (TSCs), exhibit remarkable resilience against the cytotoxic effects associated with viral infections and embryotoxic cytokines, such as TNFα and IFNγ, both of which are known to hinder blastocyst development. However, the immune properties of the preimplantation stage embryo, specifically the blastocyst, remain poorly understood. Using mouse cell model, …

Corals In Crisis: A Transcriptomic Investigation Of Stony Coral Tissue Loss Disease, Kelsey M. Beavers

Biology Dissertations - Archive

Coral reefs face existential threats due to climate change and human activities. The combined effects of ocean warming, overfishing, pollution, and habitat destruction have fundamentally altered the functionality of coral reefs and are driving a drastic increase in the prevalence and severity of coral disease outbreaks. Stony coral tissue loss disease (SCTLD) has emerged one of the most devastating disturbances to Caribbean reef ecosystems on record. Despite notable progress, the cellular mechanisms driving SCTLD pathogenesis remain poorly understood. To address this issue, my dissertation investigates the gene expression, histopathology, immune protein activity, and symbiont community dynamics involved in SCTLD progression …

Immunomodulatory Effects Of Resolvin D2 In A Model Of Infection, Prem Yugandhar Kadiyam Sundarasivarao

Graduate School of Biomedical Sciences Theses and Dissertations

Dysregulated hyperinflammatory host immune response to underlying bacterial infections is a characteristic of sepsis. In sepsis, bacteria often trigger abnormal hyperinflammatory responses which can cause multiple organ failure and if sustained can lead to an immunosuppressive phase where the host is susceptible to secondary infections caused by opportunistic bacteria like Pseudomonas aeruginosa (P. aeruginosa). In our studies, we used a 2-hit model of cecal ligation and puncture (CLP) followed by P. aeruginosa secondary lung infection to investigate cellular and molecular mechanisms in the beneficial action of resolvin D2 (RvD2). Resolvins of the D-series are a group of fatty acids known …

The Effects Of Specialized Pro-Resolving Mediator Lipoxin A4 On Pseudomonas Aeruginosa Biofilms And Interactions With Monocytes, Julianne M. Thornton

Graduate School of Biomedical Sciences Theses and Dissertations

Pseudomonas aeruginosa (P. aeruginosa) is an opportunistic pathogen known as a major cause of hospital-acquired secondary infections, commonly causing chronic respiratory infections in immunocompromised individuals, especially those with cystic fibrosis, and often found in wound infections. P. aeruginosa uses the quorum sensing pathway to readily form protective biofilms, which reduce the efficacy of antibiotics and access by host immune cells to eradicate the pathogen. Specialized pro-resolving mediators (SPMs) are lipids endogenously produced by the host immune response to infection to aid in infection resolution. One SPM, Lipoxin A4 (LxA4), has been shown to be a robust quorum sensing inhibitor.

The …

Proposing An Rna Interference (Rnai)-Based Treatment For Human Immunodeficiency Virus (Hiv) By Analyzing The Post-Transcriptional Gene Targeting Of Sars-Cov-2, Hepatitis C Virus, And A549 Lung Cancer Cells, Arjun Jagdeesh

UROP Posters

Human Immunodeficiency Virus (HIV) is a retrovirus that infects CD4+ T cell lymphocytes in humans, leading to the development of Acquired Immunodeficiency Syndrome (AIDS) if left untreated. While current treatment methods, including antiretroviral combination treatments, effectively limit HIV replication, HIV can evade these treatments due to its high mutation rate. Long-term antiretroviral treatment can also be toxic to patients, meaning patients would benefit from a new mechanism of HIV treatment. RNA interference (RNAi) is an antiviral pathway found in mammals, plants, and insects that involves a small-interfering RNA that is incorporated into a protein complex called the RNA-induced Silencing Complex …

Structural Formation And Functionality Of The Spoiie Protein In Clostridium Difficile, Rachel Siebenmorgen

Biological Sciences Undergraduate Honors Theses

My research efforts were directed toward the structure and functionality of a protein, designated SpoIIE [11], which previously has been shown to regulate C. difficile peptide utilization in addition to sporulation and toxin release. The SpoIIE protein is found in all spore-forming gram-positive bacteria and is a crucial component in activation of transcription factors and septum formation thus affecting the regulation and timing of spore development [11,12]. A truncated form of the SpoIIE protein named SpoIIE∆TM was used in an effort to determine the structure of an important but uncharacterized linker domain of the protein. If the structure and specific …

A Mechanistic Study On The Immunological Effects Of A Novel Anti-Schistosomal Compound, Caleb M. Sandall, Paul H. Davis

Theses/Capstones/Creative Projects

Schistosomiasis is a condition caused by a parasitic worm infection that is one of the primary neglected tropical diseases. It infects approximately 250 million people every year, and it causes the second largest economic impact from any parasitic disease. There exists a treatment for Schistosomiasis; however, it is ineffective against the juvenile stages of the worm. A novel drug has been developed that has been illustrated to have efficacy against all stages of worm infection. However, before this drug can be utilized, its method of action must be determined. Preliminary single cell transcriptomic data from our lab suggests that our …

Osmr Signaling Induces Tamp-Specific Bbb Dysfunction Following Autoimmune-Mediated Neutrophil Recruitment, Travis Scott Wertz

Boise State University Theses and Dissertations

Integrity of the brain microvessels that form the blood-brain barrier (BBB) is maintained through fine-tuned regulation of endothelial tight junction proteins, chiefly represented by claudin 5 and the tight junction-associated MARVEL protein (TAMP) occludin. Under proinflammatory conditions in autoimmune-mediated multiple sclerosis (MS), autoreactive effector T cells are activated in white matter regions of the brain and spinal cord and release cytokines to recruit circulating neutrophils that, in turn, release neurotoxic substances. Lack of tight junctions in peripheral blood vessels allows neutrophils to exit blood vessels unhindered, but BBB tight junctions must first be downregulated before neutrophils can transmigrate into the …

B25: Generation And Characterization Of Sars-Cov-2 Spike Protein-Pseudotyped Lentivirus Particles For Use In Neutralizing Antibody Titer Testing Of Human Serum, Luis Sanchez

Annual Research Symposium

No abstract provided.

Role Of Β-Glucan Structure In Dectin-1 Homo- And Hetero-Oligomerization In Innate Anti-Fungal Immunity, Eduardo U. Anaya

Biomedical Sciences ETDs

Dectin-1A is a C-type Lectin innate immunoreceptor that recognizes β-(1,3)-glucan, a structural component of Candida species cell walls. Dectin-1 has eight alternative splice isoforms including, A and B. Innate immunocytes can express one or both isoforms, but neither their relative responsiveness to β-glucan nor the potential for inter-isoform signaling cross-talk is well understood. In this study, we determine how the different structures of soluble β-glucans affect both isoforms and unravel how differences in glucan structure impact the earliest events in Dectin-1 signaling. Using quantitative microscopy techniques, we explored the role of glucan structure on Dectin-1A oligomerization, which is thought to …

Mesenchymal Stem Cells And Their Extracellular Vesicles: A Potential Game Changer For The Covid-19 Crisis, Dina H. Kassem, Mohamed M. Kamal

Pharmacy

Corona virus disease 2019 (COVID-19) is a global public health crisis. The high infectivity of the disease even from non-symptomatic infected patients, together with the lack of a definitive cure or preventive measures are all responsible for disease outbreak. The severity of COVID-19 seems to be mostly dependent on the patients’ own immune response. The over-activation of the immune system in an attempt to kill the virus, can cause a “cytokine storm” which in turn can induce acute respiratory distress syndrome (ARDS), as well as multi-organ damage, and ultimately may lead to death. Thus, harnessing the immunomodulatory properties of mesenchymal …

Development Of In Vitro Models To Study The Rapid Extraintestinal Dissemination Of Salmonella., Adarsh Gopinath

Electronic Theses and Dissertations

Salmonella appears in the bloodstream of mice in as little as 15 minutes after oral inoculation and establishes persistent colonies in the spleen and liver. While its pathway to blood is undetermined, this phenomenon is dependent on the activity of Salmonella pathogenicity island 2 (SPI-2) coded type III secretion system (T3SS) and CD18+ phagocytes. We hypothesize that dendritic cells associated with the basal face of the gut epithelium, that are naturally migratory and known to sample for luminal antigens directly transport Salmonella to the bloodstream. This process comprises of at least two phases, dissociation and reverse transmigration. We define dissociation …

Characterization Of A Mycoplasma Pneumoniae Cards Toxin Mutant, Nikaash Pasnoori

Honors Scholar Theses

Mycoplasma pneumoniae is a high-burden pathogen which causes mild to significant infections of the respiratory system. According to the CDC, an estimated two million cases occur yearly in the United States alone, demonstrating the widespread effect of the pathogen. In addition to being the cause of respiratory infections, M. pneumoniae has also been implicated in exacerbating pre-existing asthma conditions. These morbidities make finding a vaccine candidate a vital part of easing the healthcare burden caused by the pathogen. The current mechanism of infection is unknown, but recent evidence points to the Community Acquired Respiratory Distress Syndrome (CARDS) toxin as being …

The Histoplasma Capsulatum Ddr48 Gene Is Required For Survival Within Macrophages And Resistance To Oxidative Stress And Antifungal Drugs, Logan Blancett

Dissertations

Histoplasma capsulatum(Hc)is a systemic, dimorphic fungal pathogen that affects upwards of 500,000 individuals in the United States annually. Hc grows as a multicellular mold at environmental temperatures; whereas, upon inhalation into a human or other mammalian host, it transforms into a unicellular, pathogenic yeast. The research presented in this dissertation is focused on characterizing the DNA damage-responsive gene HcDDR48. HcDDR48was originally isolated via a subtractive DNA library enriched for transcripts enriched in the mold-phase of Hcgrowth. Upon further analysis we found that HcDDR48is not just expressed in the mold morphotype, but both growth programs …

Role Of Host Cell Β-Catenin During Toxoplasma Gondii Infection, Cameron H. Ranken

Biology ETDs

The microbial pathogen Toxoplasma gondii is an intracellular protozoan that actively invades host cells and simultaneously creates a specialized parasitophorous vacuole within which the parasite lives and replicates. The parasite molecular machinery that drives establishment of the intracellular niche is relatively well known. However, it is now emerging that Toxoplasma exploits less well-understood host cell components to enable successful infection. Here, we examined the role of host Wnt/β-catenin during T. gondii infection. Using human fibroblasts and a mouse dendritic cell line, we found that infection with Toxoplasma stimulated both upregulation and nuclear localization of β-catenin. Using a transwell experimental approach, …

Characterization Of The Protective Role Of Th17 Cells In An Fc Receptor-Targeted Vaccine Strategy Against Fracisella Tularensis Infection, Kyle Devenney

Seton Hall University Dissertations and Theses (ETDs)

Using a murine model, we have previously showed that targeting an inactivated form of F.tularensis (iFt) bacteria to Fcg receptors by utilizing an IgG2a, anti-LPS monoclonal antibody (mAb) provides 100% protection against a lethal dose with the live vaccine strain (LVS). The binding of anti-LPS monoclonal antibodies and iFt create an immune complex (mAb-iFt) allowing the Fc-region of the antibody to target Fc receptors expressed on antigen presenting cells, leading to a more robust and effective processing and presentation of the bacterial antigens. Although the resulting protective response generated relies on both humoral and cell-mediated immunity, in our study we …

Assessment Of Melanocyte-Specific Primary And Memory Autoimmune Responses In Vitiligo-Prone Smyth And Vitiligo-Susceptible, Non-Expressing Brown Line Chickens, Daniel Morales Falcon

Graduate Theses and Dissertations

Vitiligo is an acquired de-pigmentation disorder characterized by the post-natal loss of epidermal melanocytes (pigment-producing cells) resulting in the appearance of white patches in the skin. The Smyth line of chicken is the only model for vitiligo that shares all the characteristics of the human condition including: spontaneous post-natal loss of melanocytes, interactions between genetic, environmental and immunological factors and associations with other autoimmune diseases. In addition, an avian model for vitiligo has the added benefit of an easily accessible target tissue (a growing feather) that allows for the repeated sampling of an individual and thus the continuous monitoring of …

Lymphoid Hematopoiesis And The Role Of B-Cells In Transgenic Mouse Model Of Sickle Cell Disease, Christina Cotte

University Scholar Projects

Sickle cell disease (SCD) has been shown to be associated with decreased baseline immunity and thus increased susceptibility to infection. I sought to discern possible causes of this by looking into the correlations between SCD and hematopoiesis, the immune system and the neuroendocrine system, and ultimately by conducting experiments surrounding the impaired immune system of SCD. These experiments focused on the potential causes and effects of the diminution of B-1a cells in the SCD spleen. Adoptive transfers, infections with Streptococcus pneumoniae, and histologic imaging were conducted to establish if the diminution of the B-1a cells in the SCD spleen …

Endothelial Hspa12b Is A Novel Protein For The Preservation Of Cardiovascular Function In Polymicrobial Sepsis Via Exosome Mir-126, Xia Zhang

Electronic Theses and Dissertations

Sepsis is the most frequent cause of mortality in most intensive care units. Cardiovascular dysfunction is a major complication associated with sepsis, with high mortality rates up to 70%. Currently, there is no effective treatment approach for sepsis.

The integrity of the endothelium is fundamental for the homeostasis of the cardiovascular system. Sepsis induces endothelial cell injury which is the key factor for multiple organ failure. The increased expression of adhesion molecules and chemokines in endothelial cell promotes leukocytes infiltration into the tissue. The loss of tight junction proteins and increased permeability of the endothelial cells will provoke tissue hypoxia …

Characterization Of Nuclear Factor-Kappab Binding Sites In The Freshwater Snail, Biomphalaria Glabrata, Laura E. Deneckere

Lawrence University Honors Projects

Biomphalaria glabrata is an intermediate snail host for the digenean trematode, Schistosoma mansoni, which causes the human disease schistosomiasis. A lot of research has focused on the snail-schistosome interaction, especially in regards to the immune response of the snail. The nuclear factor-kappaB (NF-κB) pathway, which is involved in regulating the immune response, can be triggered by the Toll-like receptor (TLR) signaling pathway. However, not much is known about the specific molecular mechanisms regulating these responses. Both NF-κB and TLR homologues have recently been reported in B. glabrata so it is of great interest to determine if BgNF-κB can regulate …

The Differentiation And Protective Function Of Cytolytic Cd4 T Cells In Influenza Infection, Deborah M. Brown, Anna T. Lampe, Aspen M. Workman

School of Biological Sciences: Faculty Publications

CD4 T cells that recognize peptide antigen in the context of class II MHC can differentiate into various subsets that are characterized by their helper functions. However, increasing evidence indicates that CD4 cells with direct cytolytic activity (CD4 CTL) play a role in chronic as well as acute infections, such as influenza A virus (IAV) infection. In the last couple of decades, techniques to measure the frequency and activity of these cytolytic cells has demonstrated their abundance in infections, such as human immunodeficiency virus, mouse pox, murine gamma herpes virus, cytomegalovirus, Epstein–Barr virus, and influenza among others. We now appreciate …

Comparison Of Different Modulators That Affect Macrophage Activation In Vitro, Alda Alexa Díaz Pérez

Graduate Theses and Dissertations

Inflammation is known as a mechanism to regulate and control infections as well as promote tissue repair. Macrophages (Mф) are known to be a major cell type in the initiation, sustainability and resolution of inflammation. Moreover, Mф are essential for the remodeling process that is also known as the wound healing response. The objective of this research was to compare five modulators (acetylsalicylic acid (ASA), dexamethasone (DEX), prostaglandin E2 (PGE2), iloprost, and resolvin D1 (RvD1) for their anti-inflammatory effects on macrophages in vitro. Then, Mф phenotype in terms of gene expression and secreted cytokine response was determined. Our study compared …