Immunology and Infectious Disease Commons^™

+Protective Roles For Interferon-Gamma In Astrocytes During Chronic Autoimmunity, Brandon C. Smith

ETD Archive

Multiple sclerosis (MS) is an inflammatory and neurodegenerative disease of the central nervous system (CNS). Infiltrating inflammatory immune cells perpetuate demyelination and axonal damage in the CNS and significantly contribute to pathology and clinical deficits. Interferon (IFN)γ is classically described as deleterious in acute CNS autoimmunity, we and others have shown astrocytic IFNγ signaling also has a neuroprotective role. We found IFNγ signaling on astrocytes upregulates subunits of the immunoproteasome (iP) and programmed death ligand 1 (PD-L1), both of which serve protective roles during autoimmunity. Astrocyte-specific knockouts of Ifngr1 resulted in increased clinical severity in the MS murine model, experimental …

Phylogenomics Reveals The History Of Host Use In Mosquitoes, John Soghigan, Charles Sither, Silvia Andrade Justi, Gen Morinaga, Brian K. Cassel, Christopher J. Vitek, Todd P. Livdahl, Siyang Xia, Andrea Gloria-Soria, Jeffrey R. Powell, Thomas Zavortink, Christopher M. Hardy, Nathan D. Burkett-Cadena, Lawrence E. Reeves, Richard C. Wilkerson, Robert R. Dunn, David K. Yeates, Maria Anice Sallum, Brian D. Byrd, Michelle D. Trautwein, Yvonne-Marie Linton, Michael H. Reiskind, Brian M. Wiegmann

Biology

Mosquitoes have profoundly affected human history and continue to threaten human health through the transmission of a diverse array of pathogens. The phylogeny of mosquitoes has remained poorly characterized due to difficulty in taxonomic sampling and limited availability of genomic data beyond the most important vector species. Here, we used phylogenomic analysis of 709 single copy ortholog groups from 256 mosquito species to produce a strongly supported phylogeny that resolves the position of the major disease vector species and the major mosquito lineages. Our analyses support an origin of mosquitoes in the early Triassic (217 MYA [highest posterior density region: …

Effect Of Macrophage Expressed Α7 Nicotinic Acetylcholine Receptor (Α7nachr) On Migration Of Macrophages During Inflammation, Kasey Keever

Electronic Theses and Dissertations

Sepsis is a life-threatening condition characterized by overwhelming inflammation, resulting in organ system damage, leading to a high mortality rate. Care in the clinical setting is supportive, and there are no approved sepsis-specific treatments. In septic mice, activation of the cholinergic anti-inflammatory pathway decreases cytokine secretion by leukocytes and improves survival. The cholinergic anti-inflammatory pathway is a reflex of the parasympathetic nervous system, converging on the α7 nicotinic acetylcholine (α7nAChR) at the surface of macrophages. Signaling through the receptor blocks NF-kB activation, thus cytokine secretion. Receptor activation has other effects on macrophages, including modulating their migration to …

Human-Bat Interactions In A Disease Emergence Hotspot: Implications For Human Health And Bat Conservation, Reilly Tempest Jackson

Graduate Theses and Dissertations

Bats are an ecologically important taxon that can host zoonotic pathogens. Globally, many bat species are synanthropic and live closely with humans, often roosting in man-made structures. The spatial overlap between humans and bats creates opportunities for human-bat contact, which can lead to human exposure to bat-borne pathogens and conflicts that cause bat mortality. Despite this risk, little is known about the drivers and characteristics of these human-bat interactions in buildings and work is needed to understand this aspect of the wildlife-urban interface. In Chapter I, I present a literature review that identifies the geographic and taxonomic trends in reported …

Cytokine Profiles In Peruvian Pinnipeds And Their Relationships With Environmental Stressors, Mykenzee L. Munaco

All HCAS Student Capstones, Theses, and Dissertations

Large colonies of two vulnerable, sympatric pinniped species, Peruvian fur seals (Arctocephalus australis Peruvian subpopulation; PFS) and South American sea lions (Otaria byronia; SASL), reside and reproduce in Punta San Juan, Peru (PSJ) where they are exposed to stressors such as environmental contaminants and El Niño-Southern Oscillation (ENSO) events. Cytokine concentrations can be indicative of an animal’s health and immune function by allowing for immunoresponse characterization as Th1 or Th2 dominant. Utilizing an archived pinniped plasma collection of samples from 2009-2019 (n=148), 13 cytokines were analyzed in PFS and SASL: GM-CSF, IFN-γ, KC-like, MCP-1, TNF-α, IL-2, IL-6, …

Microglial Response To Glucocorticoids During Chronic Sleep Fragmentation, Christian Chelson

Masters Theses & Specialist Projects

Sleep is one of the body’s greatest and most basic needs. Chronic sleep loss (<6 hours a day) is linked to many cardiovascular issues, diabetes, and inflammatory conditions and has been shown to lower life expectancy. Obstructive sleep apnea (OSA) is a complication that causes sleep fragmentation in >8% of adults from developed countries, and many with OSA may be unaware of their condition. Having long-term OSA is linked to neuroinflammation caused by activated microglia in the brain, but the mechanics of this inflammation are not well understood. It is known that glucocorticoids, steroid hormones produced and released from the adrenal glands, have a suppressive effect on microglia. The purpose of this study is to explore the role that glucocorticoids have upon microglia activation induced by chronic sleep fragmentation (SF). C57BL/6J mice were …

Functional Analysis Of Two Campoletis Sonorensis Ichnovirus Vinnexins In Drosophila Melanogaster, Peng Zhang

All Dissertations

Campoletis sonorensis Ichnovirus (CsIV) is produced by the ichneumonid parasitoid Campoletis sonorensis (the primary host). Female parasitoid wasps restrictedly replicate viruses in their ovaries and inject them into a larval lepidopteran (secondary host) during oviposition. This symbiotic virus of C. sonorensis is essential for successful parasitization. CsIV is characterized by having a large, segmented double-stranded DNA genome with a large number of genes, many of which are associated with one of five multigene families. The CsIV vinnexin gene family is one of them and has four members, including CsIV-vnxD and CsIV-vnxG. Vinnexins are homologues of insect Innexins, which form gap …

Microsporidian Spores And The Integrin Binding Loop Of The Madam Protein Are Important For Integrin Signaling And Attachment To Host Cells, Cindy L. Barrett

Electronic Theses and Dissertations

Microsporidia are a distant fungal pathogen that have severe clinical consequences for the immunocompromised. Previous work identified a microsporidian pathogen protein termed Microsporidian ADAM or MADAM. This protein has close sequence homology to other ADAM proteins (A Disintegrin and Metalloproteinase) in two microsporidian species, Encephalitozoon intestinalis and E. cuniculi. ADAM proteins have a wide range of functions, including binding to integrins and host signaling. It is known that many pathogens manipulate integrins to invade host cells, and it is predicted that microsporidia are also exploiting this host target. Previous work with the MADAM protein demonstrated that this protein has a …

Newer Surveillance Data Extends Our Understanding Of The Niche Of Rickettsia Montanensis (Rickettsiales: Rickettsiaceae) Infection Of The American Dog Tick (Acari: Ixodidae) In The United States, Catherine A. Lippi, Holly D. Gaff, Robyn M. Nadolny, Sadie J. Ryan

Biological Sciences Faculty Publications

Background: Understanding the geographic distribution of Rickettsia montanensis infections in Dermacentor variabilis is important for tick-borne disease management in the United States, as both a tick-borne agent of interest and a potential confounder in surveillance of other rickettsial diseases. Two previous studies modeled niche suitability for D. variabilis with and without R. montanensis, from 2002-2012, indicating that the D. variabilis niche overestimates the infected niche. This study updates these, adding data since 2012.

Methods: Newer surveillance and testing data were used to update Species Distribution Models (SDMs) of D. variabilis, and R. montanensis infected D. variabilis, in …

Identification And Initial Characterization Of Hfq-Associated Srnas In Histophilus Somni Strain 2336, Bindu Subhadra, Dianjun Cao, Roderick Jensen, Clayton Caswell, Thomas J. Inzana

Faculty Publications - Biological Sciences

Small RNAs (sRNA), in association with the global chaperone regulator Hfq, positively or negatively regulate gene expression in bacteria. For this study, Histophilus somni sRNAs that bind to Hfq were identified and then partially characterized. The Hfq-associated sRNAs in H. somni were isolated and identified by co-immunoprecipitation using anti-Hfq antibody, followed by sRNA sequencing. Sequence analysis of the sRNA samples identified 100 putative sRNAs, out of which 16 were present in pathogenic strain 2336, but not in non-pathogenic strain 129Pt. Bioinformatic analyses suggested that the sRNAs HS9, HS79, and HS97 could bind to many genes putatively involved in virulence/biofilm formation. …

Effects Of Maternal Disease History On Provisioning, Brooding, And Offspring Outcomes, Sakura Roberts

Biological Sciences Undergraduate Honors Theses

Disease within a population has the ability to shape the development, evolution, and general performance of a species. Pathogen exposure to hosts can influence their physiology and behavioral patterns to further shape offspring immunity. Parental conditions experienced by offspring during early development can benefit survival and fitness (e.g. increasing provisioning rates), as well as help deter against similar diseases experienced by parents. By testing if parental behavior changes can better prepare offspring outcomes for disease exposure, such as disease severity or duration of infection, we can see the beneficial impacts it has on disease dynamics and host-pathogen processes. Incubation temperature, …

Potency Of Novel Anti-Toxoplasmic Compounds, Matthias Walters

Theses/Capstones/Creative Projects

Toxoplasma gondii, the causative agent of toxoplasmosis, is an intracellular apicomplexan parasite. Toxoplasmosis is often asymptomatic, though, it can be debilitating or fatal to immunocompromised individuals and fetuses, being one of the leading causes of fetal mortality and birth defects. Toxoplasmosis is treated with a synergistic combination of drugs pyrimethamine and sulfadiazine; however, these drugs are only effective against the acute stage of infection, and the pyrimethamine is relatively cytotoxic, damaging bone marrow and causing noxious side effects. Due to these limitations, a safer alternative that targets the chronic stage of infection is needed. In this study, we tested …

Uncovering Molecular Targets To Overcome Immunosuppression In Non-Small Cell Lung Cancer With Acquired Tki Resistance, Sonia A. Patel

Dissertations and Theses (Open Access)

Non-small cell lung cancer (NSCLC) remains the leading cause of cancer-related deaths worldwide. Targeted therapeutic agents, such as epidermal-like growth factor receptor (EGFR) tyrosine kinase inhibitors (TKIs) or monoclonal antibodies targeting vascular endothelial growth factor (VEGF/R), can effectively inhibit upregulated signaling pathways driving tumorigenesis in NSCLC and many other cancers. Unfortunately, however, resistance to such targeted therapies inevitably arise in most patients and can occur through a variety of resistance mechanisms including genomic alterations and upregulation of bypass pathways. Additionally, patients who have acquired resistance to these targeted agents typically have tumors characterized by an immunosuppressive tumor microenvironment and thus …

The Presence Of Tetracycline-Resistant Bacteria In A Kean University Campus Soil Sample, Esther Blankson, Jessica Kobilas, Gianna Medeiros

Kean Quest

The spread of antimicrobial resistance (AMR) in the environment is a worldwide problem that threatens human health. Bacteria are becoming increasingly resistant to antibiotics as the consumption of antibiotics grows. In particular, soil can be contaminated with bacteria that are resistant to antibiotics. As of today, there is no surveillance system that tracks the spread of antibiotic-resistant bacteria, however, Tufts University aims to change this by implementing the Prevalence of Antibiotic Resistance in the Environment (PARE) project. The course-based PARE project consists of research students sampling soil in diverse locations and reporting the prevalence of antibiotic-resistant bacteria. The purpose of …

The Role Of Community In Immunity Against Sars-Cov-2, Jessica Kobilas

Kean Quest

This literature review investigated the roles genes activated by social interactions had in helping to build immunity against COVID-19. Past studies have shown that individuals who are more socially connected are less likely to become ill due to social interactions strengthening the immune system through optimal exposure to bacteria and viruses in the environment. The IL-6 and TLR4 genes that are activated through social interactions and associated with cytokines have been analyzed in cases of various viral infections. Cytokines play a role in inflammation and have both pro-inflammatory and anti-inflammatory responses to infections and viruses. The results suggest that the …

Does Stress Physiology Mediate Disease Resistance In The Arizona Tiger Salamander (Ambystoma Mavortium Nebulosum)?, Megan Zerger

2023 Midwest Ecology & Evolution Conference

Amphibian biodiversity has greatly diminished in recent years due to disease. Panzootic pathogenic fungi Batrachochytrium dendrobatidis (Bd) causes the deadly disease chytridiomycosis (chytrid), a primary driver of catastrophic global amphibian declines and extinctions. The pathogenesis of chytrid is still unclear, as certain species and individuals within a species are differentially affected. Susceptibility and mortality of Bd are influenced by prolonged chronic stress. Prolonged glucocorticoid activity deleteriously affects many of the same physiological processes as Bd infections, and corticosterone is the primary glucocorticoid released by amphibians in response to stress. Thus, the objective of our study is to assess …

Mir125a As Molecular Target Of Vitamin D Mediated Inhibition Of Cd4+ T Cell Differentiation Into Th17 Cells In Mrl/Lpr Lupus-Prone Mice, Miranda Hilt

Undergraduate Distinction Papers

The dynamic function of vitamin D in an array of immunomodulatory and anti-inflammatory mechanisms and its implication in the pathogenesis of autoimmune diseases has been the topic of much recent scholarship. Here I attempt to elucidate the molecular mechanism of vitamin D-mediated inhibition of the differentiation of CD4+ T cells into pro-inflammatory Th17 cells in MRL/lpr lupus prone mice by investigating how miR-125a expression is affected by dietary modulation of cholecalciferol (vitamin D₃). MRL/MpJ and MRL/lpr mice were split into three experimental groups and fed specially formulated diets that varied in their concentrations of vitamin D. …

The Effect Of Bisphenol A (Bpa) Substitutes On Cd4+ T Cell Immunity, Cassandra Poole

Longwood Senior Theses

CD4+ helper T cells are an important cell of the immune system. One key factor in the mediation of the immune system in general, and T cells in particular, is the female sex hormone estrogen. Abnormal estrogen levels are associated with a variety of conditions, including autoimmune diseases, and several types of cancer, including breast cancer. BPA is a well-known estrogen mimicking compound, used in the manufacturing of plastics, epoxy resins, and polystyrenes. As the negative effects of BPA become more apparent, many BPA substitutes have been developed. While the effect of estrogen on T cells is understood, the effect …

Role Of Nod2 Receptor In Immune Response To Staphylococcus Aureus, Precious Mckenzie, Aparna Palakodeti Ph.D

Research Days

Staphylococcus aureus, a gram-positive, commensal bacterium, causes several opportunistic diseases and infections in humans. Furthermore, some strains of S.aureus have developed resistance to antibiotics such as methicillin and pose a health risk. Pattern Recognition Receptors (PRRs) on host immune cells recognize specific components of S.aureus cell wall and mount an immune response against the bacteria. One such PRR is the Nuclear Oligomerization Domain 2 (NOD2) receptor which is present in the cytosol of host immune cells. NOD2 recognizes Muramyl-Dipeptide (MDP), a component of the peptidoglycan cell wall of several bacteria including S. aureus. The binding of MDP to NOD2 allows …

Histone Deacetylase 8 Is A Novel Therapeutic Target For Mantle Cell Lymphoma And Preserves Natural Killer Cell Cytotoxic Function, January M. Watters

USF Tampa Graduate Theses and Dissertations

This study demonstrates for the first time that HDAC8 function is critical for MCL survival, and abrogating its activity in human primary NK cells does not interfere with NK IgG antibody directed ADCC therapies ex vivo. Human NK cells, isolated from healthy donors, are highly resistant to HDAC8 inhibitor treatment with PCI-34051. Even at the highest concentration, 20uM, no toxicity was observed. Conversely, MCL cell lines representative of the aggressive MCL subtype, classical MCL, were especially sensitive to PCI-34051, an HDAC8 selective inhibitor, treatment. Blocking HDAC8 activity and/or abrogating expression through shRNA silencing induced significant DNA damage, hyperacetylation of SMC3, …

Rna Virus-Mediated Changes In Organismal Oxygen Consumption Rate In Young And Old Drosophila Melanogaster Males, Eli Hagedorn, Dean Bunnell, Beate Henschel, Daniel Smith Jr, Stephanie Dickinson, Andrew Brown, Maria De Luca, Ashley Turner, Stanislava Chtarbanova

Research, Publications & Creative Work

Aging is accompanied by increased susceptibility to infections including with viral pathogens resulting in higher morbidity and mortality among the elderly. Significant changes in host metabolism can take place following virus infection. Efficient immune responses are energetically costly, and viruses divert host molecular resources to promote their own replication. Virus-induced metabolic reprogramming could impact infection outcomes, however, how this is affected by aging and impacts organismal survival remains poorly understood. RNA virus infection of Drosophila melanogaster with Flock House virus (FHV) is an effective model to study antiviral responses with age, where older flies die faster than younger flies due …

Shell Shocked: The Effects Of Stress And Bacterial Challenges On The Chelonian Innate Immune Response, Alyssa Hartzheim

Student Theses and Dissertations

In the realm of immunology, the use of reptilian models remains low in comparison to their mammalian counterparts. Consequently, much of the inner workings of reptilian immunity remain to be elucidated. Specifically, chelonian species are vastly understudied. In the past decade, research focusing on reptilian immunology has increased. This thesis seeks to contribute to the growing body of work concerning immune trade-offs. I studied reptilian innate immune ability in both captive and free-living populations with consideration of both intrinsic and extrinsic factors. In the zoo-housed Indian star tortoises (Geochelone elegans) and northern spider tortoises (Pyxis arachnoides brygooi), I demonstrated species-specific …

Tgf-B Signaling Mechanisms In Caenorhabditis Elegans Response To Bacterial Pathogens, Emma J. Ciccarelli

Dissertations, Theses, and Capstone Projects

When exposed to infection, the nematode C. elegans mounts an innate immune response through secretion of antimicrobial peptides (AMPs). Different signaling pathways in the worm regulate release of these AMPs. One highly conserved pathway is the C. elegans BMP like pathway – regulated by the ligand DBL-1. The DBL-1 pathway is noted for its significant role in development but has also been shown to regulate many post-developmental processes within the worm, including the immune response. We are interested in determining how DBL-1 signaling can mediate a response specific to immunity, separate from its other functions in the worm. Through survival …

The Impacts Of Immune Challenges On Fish Behavior And Physiology, Teisha King

LSU Doctoral Dissertations

For species living in dominance hierarchies, social rank dictates access to resources and often contributes to reproductive success. To ensure survival, individuals constantly evaluate trade- offs between crucial biological systems, like the reproductive and immune systems, depending on their social rank and physiological state. Little is known about how social species balance interactions between immune system function, fluctuations in social status and reproductive fitness, and the performance of behaviors necessary for maintaining social status when sick, particularly in fishes, the largest and most diverse group of vertebrates. My dissertation research uses a whole animal approach to examine how physiological profiles …

Molecular Regulation Of The Salicylic Acid Hormone Pathway In Plants Under Changing Environmental Conditions, Christina A. M. Rossi, Eric J. R. Marchetta, Jong Hum Kim, Christian Castroverde

Biology Faculty Publications

Salicylic acid (SA) is a central plant hormone mediating immunity, growth, and development. Recently, studies have highlighted the sensitivity of the SA pathway to changing climatic factors and the plant microbiome. Here we summarize organizing principles and themes in the regulation of SA biosynthesis, signaling, and metabolism by changing abiotic/biotic environments, focusing on molecular nodes governing SA pathway vulnerability or resilience. We especially highlight advances in the thermosensitive mechanisms underpinning SA-mediated immunity, including differential regulation of key transcription factors (e.g., CAMTAs, CBP60g, SARD1, bHLH059), selective protein–protein interactions of the SA receptor NPR1, and dynamic phase separation of the recently identified …

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 …

Tissue And Sex-Dependent Regulation Of Innate Immunity And Rna Editing In Mice, Kelsey R. Kendrick

Graduate Theses/Dissertations

Inflammation occurs as a result of insult or infection within the body. Individual cells respond to inflammation by upregulating genes that help mediate the immune response, such as ADAR1. ADAR1 helps regulate the immune response but also catalyzes a process called RNA editing. RNA editing alters the sequence of select mRNAs to alter the encoded proteins. The result is altered function of the encoded protein, which is often beneficial for the cell. Our goal was to determine how inflammation affects the function of ADAR1. Since we know that the effects of inflammation vary between different organs and sexes, we examined …

The Effect Of Larval Competition On Adult Life History Traits And The Immune Response Of Adult Cat Fleas (Ctenocephalides Felis), Piper N. Zellner, Lisa D. Brown

Honors College Theses

In holometabolous insects, conditions during the larval stage can affect the adult stage. For instance, in mosquitoes, reduced larval food and high density can make adults more susceptible to infection. Fleas (Siphonaptera), like mosquitoes, go through complete metamorphosis and have adult stages that exclusively feed on the blood of vertebrates, including humans. However, flea larvae have chewing mandibles and rely on nutrients from dried fecal matter containing vertebrate blood proteins. Their limited mobility and unique nutritional needs confine their development to specific areas, likely leading to frequent larval competition in natural conditions. Yet, the influence of larval density on the …

Corrigendum: Characterization Of A Novel Transitional Group Rickettsia Species (Rickettsia Tillamookensis Sp. Nov.) From The Western Black-Legged Tick, Ixodes Pacificus, David T. Gauthier, Sandor E. Karpathy, Stephanie L. Grizzard, Dhwani Batra, Lori A. Rowe, Christopher D. Paddock

Biological Sciences Faculty Publications

No abstract provided.

Examining The Immune Regulation Of Nlrp12 Through Novel Protein Interactions, Catherine Rippe

Graduate Theses/Dissertations

NOD-like receptors (NLRs) are intracellular proteins that play an important role in the regulation of the innate immune response to pathogens. Since being identified, various functions for NOD-like receptor pyrin domain containing 12 (NLRP12) have been suggested. It has been shown to negatively regulate the inflammatory response through canonical and noncanonical NF-kB signaling pathways, control tumorigenesis and gut homeostasis and exacerbate inflammation through the formation of a multi-protein complex called an inflammasome. Due to the varying roles established for NLRP12, the mechanisms by which it functions remain poorly understood. In this study, I sought to confirm a novel protein-protein interaction …