Immunity Commons^™

Examining The Ligands, Location, And Function Of Toll-Like Receptor 10, Kiefer Keanu Tam

Master's Theses

Toll-like receptors are a class of innate immune pattern recognition receptors that detect pathogen-associated molecular patterns and regulate downstream inflammatory responses. Toll-like receptor 10 remains the only human TLR whose ligand specificity, cellular localization, and immunological function are not fully defined. Emerging evidence suggests that TLR10 may play an anti-inflammatory role and can heterodimerize with TLR2 to modulate immune signaling. Previous studies from our laboratory demonstrated that stimulation with heat-killed Mycobacterium tuberculosis promotes TLR2-TLR10 heterodimerization and trafficking to the cell surface. In this study, we expanded our ligand panel to include additional gram-positive bacteria, particularly anti-inflammatory probiotic species, to further …

Harnessing The Gut-Diet Axis To Enhance Chemotherapy And Immunotherapy, Jill Carline

Bryant REDay (Research and Engagement Day)

The human microbiome, a complex ecosystem of trillions of microorganisms including bacteria, fungi, and viruses, represents a critical "gut-diet axis" that significantly influences cancer progression and therapeutic efficacy. While a state of homeostasis supports systemic immunity, dysbiosis is linked to chronic inflammation and can actively promote resistance to standard cytotoxic chemotherapies and modern immune checkpoint inhibitors. Specifically, research indicates that Bacteroides fragilis (ETBF) promotes resistance to 5-Fluorouracil and Oxaliplatin in colorectal cancer by activating Notch1 receptors to inhibit apoptosis and push cancer cells into a resilient, stem-cell-like state. Conversely, the introduction of fiber-rich and fermented foods can cultivate beneficial bacteria …

Tlr3 Mediated Type I Interferon Response In Mammalian Cell Defense Against Cryptosporidium Parvum Infection., Anjelica Matias

Biochemistry and Molecular Biology

Cryptosporidium parvum is a major cause of a diarrheal disease which affects many children in the USA as well as the rest of the world, yet the contribution of its double stranded RNA (dsRNA) viral symbiont, Cryspovirus (CSpV1) to host innate immunity remains unclear. This study investigated whether CSpV1 activates Toll Like Receptor 3 (TLR3) signaling pathways and downstream Interferon type I (IFN I) responses in mammalian intestinal epithelial cells. Confluent Human Ileocecal Colorectal Adenocarcinoma cells (HCT8) were exposed to CSpV1, and the expression levels of Tumor Necrosis Factor Receptor-Associated Factor 3 (TRAF3), Nuclear Factor-𝜅-light chain enhancer of activated B-cells …

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 …

Expanding Inducible Epithelial Resistance Against Pneumonia: Novel Virus, Novel Receptor, Michael Longmire

Dissertations and Theses (Open Access)

Pneumonia is the leading infectious cause of death worldwide and presents a continuing risk among immunocompromised patients. Our work has been focused for many years on the phenomenon of inducible epithelial resistance, where activation of the innate immune response in the airway epithelium is necessary and sufficient to produce a pathogen-killing but self-protective environment to prevent severe disease. Inducible resistance is pathogen-agnostic and has been demonstrated against an array of respiratory infections. We achieve this using a combination of pattern recognition receptor agonists – Pam2CSK4 and ODN M362 being the current formulation – which produce synergistic levels of pathogen reduction …

Clinical Characteristics And Outcomes Of Pediatric Staphylococcal Scalded Skin Syndrome (Ssss) At An Inner-City Tertiary Care Center, Nina Kb Gust Md, Ashley Frei Bs, Rebecca M. Adams Bs, Elika Ridelman Phd, Christina Shanti Md, Ronald Thomas Phd, Jocelyn Y. Ang Md

Medical Student Research Symposium

Introduction

Staphylococcal Scalded Skin Syndrome (SSSS) is a blistering skin condition caused by a toxin-producing staphylococcus species. Epidemiologic studies on pediatric SSSS in the United States are limited, with a reported incidence of 7.67 cases per million children and 45.1 per million infants. Immature renal function, lack of protective antibodies, and increased exotoxin target desmoglein-1 are hypothesized to increase incidence in younger children. We aimed to determine clinical and microbiological characteristics of pediatric SSSS and factors that could help predict disease severity.

Methods

A retrospective chart review was performed for admitted patients under 18 years old diagnosed with SSSS from …

Genetic Analysis Of Methionine Restriction-Associated Mitochondrial Unfolded Protein Response Signaling., Josh D. Dodge

Biology Dissertations - Archive

The lifespan of an organism is dictated by various genetic and environmental factors. One such determinant is the health of mitochondria which are organelles that mediate various critical cell functions including a significant role in generating the vast supply of cellular energy. Indeed, the gradual decline of mitochondrial function is believed to be a hallmark and possible cause of aging. Paradoxically, mild mitochondrial dysfunction early in life extends lifespan in various model organisms. Cells use diverse approaches to promote mitochondrial homeostasis, including the transcriptional reprogramming of cells by mitochondrial unfolded protein response (UPRmt) to mitigate mitochondrial stress. Consistently, UPRmt activation …

Novel Infection By Mucor Hiemalis Kills Caenorhabditis Hosts Through Intestinal Perforation, Jay Ni

West Chester University Graduate Theses, Dissertations, and Final Projects

The nematode Caenorhabditis elegans has emerged as a popular model system to investigate cell biology and host-pathogen interactions. Presently, C. elegans is studied as a natural host of intracellular pathogens such as microsporidia and Orsay virus along with extracellular bacterial and fungal pathogens. The use of C. elegans as a model in host-pathogen research is limited by the number of naturally occurring pathogens to the organism. Through a sampling project to identify new pathogens of C. elegans, we identified the fungus Mucor hiemalis as a pathogen of Caenorhabditis species. We observed the fungus in the intestinal lumen of wild-caught …

Interactions Of The Sars-Cov-2 Viral Genome 3’-Untranslated Region With Viral And Host Rnas, Caleb Frye, Mihaela Rita Mihailescu

Electronic Theses and Dissertations

This dissertation focuses on the characterization of RNA-RNA interactions within the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) genome and with host microRNAs. As the causative agent of coronavirus disease 2019 (COVID-19), SARS-CoV-2 has evolved rapidly since its appearance. This has warranted prompt characterization of the virus particularly of its single stranded RNA (ssRNA) genome. By using a combination of bioinformatics, biophysics, and/or biological assays, we analyzed the SARS-CoV-2 viral genomic RNA and uncovered interactions of genomic RNA with host RNAs, highlighting an underutilized method of targeting RNA viruses. We showed here that the conserved elements in the viral genomic …

Host-Microbiome Interactions In The Teleost Brain, Amir Mani Varnoosfaderani

Biology ETDs

This dissertation investigates host-microbial interactions within the teleost brain, previously considered sterile. Reviewing current literature highlights significant gaps in understanding teleost brain immunity, despite prevalent neurotropic diseases. We mapped the immune profiles of rainbow trout brains and meninges, revealing the olfactory bulbs as the immune effector part of the brain and the optic tectum as a nod2 expression hub. High il6 and il10 levels were noted in the telencephalon. A persistent bacterial community within healthy salmonid brains shares diversity with gut and blood microbiota. Brain bacterial isolates exhibit genomic signatures for brain colonization and polyamine biosynthesis. The microbiota shifts across …

Establishment Of Bacteroides In The Gut And Its Role In The Cystic Fibrosis Gut-Lung Axis, Rebecca A. Valls

Dartmouth College Ph.D Dissertations

In the quest to understand the complex interplay between the gut microbiota and cystic fibrosis (CF), a disease characterized by chronic upper respiratory complications and an exacerbated proinflammatory response, our lab engaged in a collaborative study with Dartmouth-Hitchcock Medical Center (DHMC) to characterize the gut microbiota of pediatric CF patients. Initial analyses established a connection between gut microbial composition and respiratory health, particularly highlighting a scarcity of Bacteroides species compared to healthy controls. In following investigations, we utilized random forest models to understand how stool microbiota may influence clinical outcomes of these pediatric CF patients, including: age, upper respiratory infections, …

A Potential Of Watercress Nasturtium Officinale Bioactive Compounds In Inhibiting Infectious Myonecrosis Virus (Imnv) By Targeting Rna-Dependent Rna Polymerase (Rdrp) Virus From Several Countries: In Silico Approach, Qurrota A’Yunin, Fatchiyah Fatchiyah, Maftuch Maftuch, Feri Eko Hermanto, Muhammad Hermawan Widyananda, Narendra Santika Hartana, Muhaimin Rifa’I, Yoga Dwi Jatmiko

Karbala International Journal of Modern Science

Infectious myonecrosis virus (IMNV) disease causes mass mortality and decreased shrimp production. The RdRp region projects to the interior, where it may function in transcription. The focus of this study was to determine the effect of amino acid polymorphisms from several countries on the structure of RdRp and identify the potential of watercress in inhibiting IMNV by targeting the RdRp protein of IMNV through an in silico approach. The results showed that the structure of the IMNV RdRp protein from Indonesia was similar to Mexico, and the protein structure from India_QDN was identical to India_QIL. Ligand binding affinity values showed …

Antimicrobial Activity Of Cat Flea (Ctenocephalides Felis) Gut Proteins On Different Days After Blood Feeding, Dhruva K. Karnik

Honors College Theses

Cat fleas (Ctenocephalides felis) are a blood-feeding ectoparasitic insect and a common domestic pest found throughout the world. Because of their reliance on host blood, fleas are exposed to blood-borne pathogens; however, the flea gut lumen is a hostile environment for microbial colonization. For example, the gut epithelia differentially express immune genes in response to feeding. In the present study, we measured the antimicrobial activity of gut proteins from cat fleas at different days after feeding (2, 5, 7, and 14). Dissected flea guts were homogenized, passed through a syringe filter, and measured in a protein assay kit. …

Cultivating Excellence: A Literature Review On Harnessing The Power Of The Gut Microbiome For Athletic Performance, Maya Katharine Dean

Honors Projects

The interplay between our gut microbiome and health is immense. This literature review analyzes the current research assessing the interplay between gut microbiome and athletic performance. Knowing how to improve gut microbial diversity via nutrition and supplementation can take athletic performance to the next level; namely improvements in immune, mental, and physical health.

Revolutionizing Our Understanding Of Specific Platelet-Pathogen Interactions, Hammodah Rawhi Hammodah Alfar

Theses and Dissertations--Molecular and Cellular Biochemistry

Aside from their classical role in maintaining hemostasis, platelets are considered first-line vascular guardians that influence both the innate and adaptive immune systems. This is mediated by either direct interactions with immune cells or through the release of pre-stored cytokines and chemokines upon interacting with pathogens such as viruses. While this establishes platelets as potential players in the response to pathogens, it remains unclear what platelets can do with pathogens and how important that is to immune responses, especially against viruses. Most systemic viremias, such as HIV-1, present with mild thrombocytopenia, which is mediated through several mechanisms such as a …

Sars-Cov-2 Immunogenicity Models Inform Novel Strategies That Can Improve Mrna Vaccines, Katherine S. Lee

Graduate Theses, Dissertations, and Problem Reports (ETD)

The onset of the 2020 COVID-19 pandemic, caused by the novel coronavirus SARS-CoV-2, issued a call to action in the fields of biomedical science and public health to implement strategies to contain and protect against the viral threat. In record times, pharmaceutical companies produced antiviral therapies and novel mRNA vaccines that were approved by the FDA for human use. With time, these vaccines were able to assist in ending the pandemic. However, time also showed the limits of mRNA vaccine induced immunity. Despite antibody responses being initially robust, titers dramatically wane with time and are limited in cross-neutralizing ability. As …

Sars-Cov-2: Tale Of A Microscopic Murderer, Josiah P. Garner

Quest

Independent Study

Research in progress for BIOL1406: Biology for Science Majors I

Faculty Mentor: Amina Tassa, Ph.D.

I am delighted to introduce Josiah Garner’s “SARS-CoV-2: Tale of a Microscopic Murderer.” This independent study assignment explores the impact of a novel, deadly, and worldwide virus. The assignment also examines the fast development of vaccines to control the spread and reduce the symptoms of the virus.

Josiah’s paper focuses on the early history of the emergence of COVID-19, the world response, and vaccine development. He demonstrates critical thinking skills and effectively utilizes various research methods to obtain and communicate his information. Josiah …

Evaluating The Role Of The Bovine Vaginal Microbiome In Neonatal And Maternal Health Outcomes, Riley D. Messman

Theses and Dissertations

The dam vaginal microbiota is the first major microbial inoculating community within the neonate. The composition of the dam vaginal microbiota has implications in calf commensal microbiota development. Alterations of the dam microbial community prior to parturition could alter inoculating communities and immune responses in both the dam and calf. Thus, authors aimed to elucidate the microbial community composition of the bovine dam vaginal and calf nasal microbiota post-partum after utilizing betadine lavages (BL). The dam vaginal and calf nasal microbial communities and immune responses were evaluated at 0-, 15-, 30- and 60-day post-partum. Microbiota composition of the dam haircoat, …

Molecular Mechanisms Behind Sars-Cov-2 Induced Host Genome Restructuring, Erin Simpson

Dissertations and Theses (Open Access)

Severe Acute Respiratory Syndrome Coronavirus -2 (SARS-CoV-2) has caused unprecedented morbidity and mortality worldwide. There are two pathophysiological hallmarks associated with severe patient outcomes after SARS-CoV-2 acute infection, namely delayed/weakened interferon production and overactive inflammatory responses. Our previous work has shown that these altered immune responses are due, at least in part, to significant alterations in 3D genome organization and epigenetic landscape following SARS-CoV-2 infection that are distinct from and more severe than changes caused by other viral infections or immune stimulants. While these changes at the chromatin level are important for understanding the immune dysregulation seen in some cases …

Elucidating Mechanisms Involved In Host Microbial-Tumor Interactions, Vidhi Chandra

Dissertations and Theses (Open Access)

Cancer is a rising cause of mortality worldwide. Microbiota is the collection of micro-organisms that live inside our bodies and can impact the host health and disease by interacting with the immune and metabolic systems. The relationship between the microbiota and cancer is complex. Gut and intratumoral microbiota can affect cancer development and progression by influencing patient outcomes and therapy responsiveness in several cancer types. Pancreatic ductal adenocarcinoma (PDAC) is an aggressive cancer surrounded by a highly immuno-suppressive tumor microenvironment (TME) which limits efficacy of most available therapies. The tumoral niche provides a privileged microenvironment for microbial colonization that can …

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 …

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 …

Sex-Dependent Effects Of Induced Acute Inflammation On Glucose Homeostasis And Rna Editing Enzymes, Christian A. Rivas

Graduate Theses/Dissertations

The first line of defense against bodily insults, like pathogen invasion, is the innate immune system. Innate immunity sets in motion countless cascades that result in inflammation. Inflammation simultaneously affects multiple biological processes like metabolism and gene expression. Males and females react differently to inflammation. To understand both molecular and physiological sex differences in inflammation, we examined how inflammation affects gene expression and glucose metabolism. Adenosine deaminase acting on RNA (ADAR1) is upregulated by inflammation and catalyzes RNA editing, a process where nucleotides encoded by the genome are modified. ADAR1 also controls the innate immune reaction by decreasing activity of …

Neural Stem Cells: Age-Dependent Outcomes During Viral Infections In The Central Nervous System, Manisha N. Chandwani

Electronic Theses and Dissertations

Viral infections in the central nervous system (CNS) are associated with neurodevelopmental and neurobehavioral deficits. The outcomes of viral infections can be driven by damage and death of neurons. Neural stem cells (NSCs) play key roles in neurodevelopment, repair, and physiological brain function. During a viral infection, NSC activity can disturbed by direct infection of NSCs by the virus or by anti-viral immune response. Here, we aimed to assess whether the anti-viral immune response can impact NSC activity during an immunocompetent response in the adult brain. We utilized a transgenic mouse model of Measles virus infection where only the CNS …

Factors Affecting The Antibacterial Activity Of Cefiderocol On Klebsiella Pneumoniae With Diverse Characteristics, Lana Jamal Rashed Daoud

Theses

Antimicrobial resistance (AMR) is a growing serious threat that poses a burden on the healthcare system. Spread of AMR bacteria limits treatment options; thus, new antimicrobial agents are required. Cefiderocol (CFDC) is a novel siderophore cephalosporin, approved by the FDA in 2019 for use in treating infections caused by multi-drug resistant (MDR) pathogens; but it is not yet in clinical use in the UAE. CFDC is equipped with stabilizers against β-lactamases as well as a siderophore side chain that allows it to penetrate the outer membrane of bacteria through the iron uptake pathways. The aim of this study is to …

Aggregatibacter Actinomycetemcomitans Exploits And Modulates The Immune Response By Human Neutrophils For Survival In The Anaerobic Environment., Hazel Ozuna

Electronic Theses and Dissertations

Aggregatibacter actinomycetemcomitans (Aa) is a Gram-negative facultative anaerobe and an opportunistic oral pathogen, strongly associated with localized periodontitis and other inflammatory diseases. Periodontitis is a chronic inflammation of the periodontium resulting from the inflammatory response of the host towards the dysbiotic microbial community present at the gingival crevice. The host immune response creates a hostile environment for microorganisms; therefore, it is important for Aa to be able to regulate the necessary genes to survive and thrive in such an environment. Aaexpresses several virulence factors such as a cytolethal distending toxin (Cdt), lipopolysaccharide (LPS) and leukotoxin A (LtxA), …

Time Course Investigation Of The Dermal Leukocyte Response To Lipoteichoic Acid In Chickens, Ian Gilbert

Animal Science Undergraduate Honors Theses

Lipoteichoic acid (LTA) is component of the cell wall of Gram-positive bacteria that stimulates inflammation during bacterial infection. However, few studies have investigated the in vivo immune response to LTA, and none of the in vivo studies done have been performed in birds. For this project, the pulp (a skin-derivative) of growing feathers (GFs) of chickens were used as a test site to investigate the in vivo effects of intradermally injected LTA. In Study 1, the pulp of 12 GFs of 11-week-old Light-brown Leghorn (LBL) males were injected with 10 μL of differing concentrations of LTA (0.1, 1.0, 10, 100 …

Response And Molecular Control Of Cd8 T Cells During Infection And Cancer, Nicholas K. Preiss Dr.

Dartmouth College Ph.D Dissertations

CD8 T cells are potent immune effector cells capable of vast clonal expansion and clearance of infected or cancerous cells. After control of the pathogenic insult, CD8 T cells develop into quiescent, long-lived memory populations that are poised to mediate rapid protection upon reencounter with cognate antigen. These properties make control of CD8 T cell responses a highly desirable outcome of vaccine strategies and immunotherapy. Therefore, understanding how the effector function and memory differentiation of CD8 T cells are controlled at a molecular level is of great importance. In the context of infection with gammaherpesviruses (γHV), which form a latent …

Antibiotic Permeation In Gram-Negative Bacteria And Contribution Of Inflammasome Activation And Pyroptosis In Pathogenesis Of Salmonella Systemic Infection, Ankit Pandeya

Theses and Dissertations--Chemistry

Antibiotic resistance is one of the major global issues in the field of public health and medicine. Good antibiotic candidates need to be selectively toxic, inhibit cellular target, and effectively penetrate and accumulate in bacterial cells. The last factor is a formidable barrier in the development of antimicrobials effective in Gram-negative bacteria, due to the presence of two layers of cell envelope. The first half of my thesis focuses on understanding the permeation of small molecules through this formidable cell envelope, distribution inside the cell of Gram-negative bacteria, and design of novel methods to make small molecules effectively cross the …

Trained Immunity Enhances The Immune Response And Maintains Microbiome Diversity In Aging And Sepsis, P. Spencer Gill

Electronic Theses and Dissertations

The global population is rapidly aging. It is estimated that over the next thirty years, the number of individuals >60 years of age will increase by over a billion, and the number of individuals over age 80 may increase by 300 million. As humans age, our immune system becomes progressively weaker through a process called immune senescence. This age-related decrease in immune function increases susceptibility to infection and chronic diseases. Sepsis is a leading cause of death worldwide. Over the past two decades, there has been an increased incidence of sepsis which is due, in part, to our aging population …