Immunity Commons^™

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 …

Dickkopf1(Dkk1): A Novel Endogenous Ligand To Prime Nlrp3 Inflammasome Via Tlr4, Theingi Aung

Theses and Dissertations

Dickkopf1(DKK1) is a quintessential Wnt antagonist and immunomodulator in various inflammatory diseases. The underlying molecular mechanisms of DKK1-mediated immunomodulation remain elusive. Here, we identified TLR4 as a new receptor for DKK1 to activate NFκΒ pathway-mediated gene expression and pyroptosis via NLRP3 inflammasome in human and mouse macrophages.

DKK1 employed TLR4 to initiate NFκB signaling cascade via MyD88. MyD88-TAK1-NFκΒ pathway activation by DKK1 increased HIF1α, NFκB, and NLRP3 protein expression levels, leading to pyroptosis. Unlike LPS, DKK1 did not induce IRAK4 phosphorylation, while the interaction between MyD88 and IRAK4 was maintained for downstream signaling activation. DKK1 did not induce IRF3 phosphorylation …

Immune Pathway Modulation In Melanoma Using Chitosan Nanoparticle-Mediated Dsrna Delivery, Bethel C. Iwuji

Theses and Dissertations (Comprehensive)

Cancer is a group of diseases characterized by abnormal and uncontrolled cell division, which typically results in the formation of tumours. Even with advances in treatments, cancer remains one of the leading causes of death globally. Melanoma is an aggressive form of skin cancer which is highly malignant, develops in the pigment-producing cells of the skin, melanocytes, and in the late stages of the disease poses a significant challenge for therapeutic intervention due to its multidrug resistance. The innate immune system is the first line of defence against invading pathogens, including viruses, bacteria, and fungi, and can recognize and destroy …

Npr1 As A Temperature-Sensitive Regulator Of Pipecolic Acid-Mediated Plant Systemic Immunity, Spencer Tout

Theses and Dissertations (Comprehensive)

Healthy plant development requires balancing both abiotic (e.g. climate) and biotic (e.g. pathogen) challenges, which intercept important signaling pathways in plants. For example, climate change-associated elevated temperature can negatively modulate various aspects of plant immunity, including the production of central immune signals salicylic acid (SA) and N-hydroxypipecolic acid (NHP). Since SA and NHP signaling both require the master immune co-activator protein NON-EXPRESSOR OF PATHOGENESIS-RELATED GENES 1 (NPR1), it is important to investigate NPR1 as a potentially temperature-regulated molecular hub. Although the NPR1 gene is not transcriptionally downregulated at elevated temperatures (28° C vs. 23° C), little is known about …

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 …

Timigp: A Computational Framework To Determine The Tumor Immune Microenvironment Associated With Prognosis And Immunotherapy Response, Chenyang Li

Dissertations and Theses (Open Access)

Accumulating evidence has suggested that the tumor immune microenvironment (TIME) drastically impacts cancer patients’ clinical outcomes, including prognosis and immunotherapy response. However, understanding TIME remains challenging due to its complexity and heterogeneity. In this dissertation, we introduce TimiGP (Tumor Immune Microenvironment Illustration based on Gene Pairs), a computational framework designed to address this challenge. Leveraging single-cell RNA-seq (scRNA-seq) and bulk gene expression data alongside clinical information, TimiGP constructs a cell-cell interaction network that elucidates the relationship between immune cell function and relevant clinical outcomes, such as prognosis and treatment response. With immunological insights, these cell-cell interactions also facilitate the development …

The Role Of Lifr Signaling In Innate Immunity, Laura Kahn Serrudo

Dissertations and Theses (Open Access)

The localized signals that bone marrow (BM) hematopoietic stem cells (HSCs) and immune cells receive are critical in regulating their responses in the steady state and inflammation. Monocytes are an abundant and key population in the innate immune response that originates in the BM, and they circulate to monitor the periphery. Monocytes are composed of many subsets that have essential and specific functions, including swift egress from the BM, production of pro-inflammatory cytokines, and differentiation into monocyte-derived dendritic cells (MoDCs), which are required for efficient pathogen eradication.

Here, we uncovered LIFR (leukemia inhibitory factor receptor) restrains low-grade chronic inflammation in …

Modulation Of Monocyte Effector Functions And Gene Expression By Human Cytomegalovirus Infection, Matthew Planchon, Jay Fishman, Joseph El Khoury

SKMC Student Presentations and Publications

Monocytes are crucial players in innate immunity. The human cytomegalovirus (CMV) infection has significant impacts on monocyte effector functions and gene expression. CMV, a β-herpesvirus, disrupts key monocyte roles, including phagocytosis, antigen presentation, cytokine production, and migration, impairing their ability to combat pathogens and activate adaptive immune responses. CMV modulates monocyte gene expression, decreasing their capacity for antigen presentation and phagocytosis while increasing pro-inflammatory cytokine production, which can contribute to tissue damage and chronic inflammation. CMV also alters monocyte migration to sites of infection while promoting trans-endothelial migration, thus aiding viral dissemination. Additionally, the virus affects reactive oxygen species (ROS) …

Sounding The Alarm: Local Cues That Drive Functional Specialization Of Brain Resident Memory T Cells, Shawn Christopher Musial Jr.

Dartmouth College Ph.D Dissertations

Resident memory T cells are a unique subset of memory T cells that persist within tissues throughout the body, including the brain, optimally positioned to exert local immune activation. Broadly, T cells in the CNS are implicated in a range of neurologic disorders, can protect against reinfection, and even participate in normal CNS homeostasis. Despite this, there remain significant gaps in knowledge about how T cells, specifically resident memory T cells (T_RM), are regulated and function in the unique CNS environment. Here, we leverage a mouse model of acute viral infection to dissect the diversity of brain T …

Dying Right: Supporting Anti-Cancer Therapy Through Immunogenic Cell Death, Elizabeth Schmitz

Theses & Dissertations

The primary goal of most anti-cancer therapy is to eradicate neoplastic cells. Simultaneously, neoplastic cell death is the first step of the cancer-immunity cycle, which starts with the release of antigens from cancer cells and ends with T-cell directed killing of cancer cells, in addition to long-standing memory to tumor antigens encountered. Immunogenic damage-associated-molecular patterns (DAMPs) are endogenous cell molecules repurposed in times of insurmountable cell stress (e.g., CALR, ATP, HMGB1) to facilitate communication between dying cells and adaptive immune cells, acting as adjuvants for the cancer-immunity cycle, in a cellular fate termed immunogenic cell death (ICD). It …

Lactoferrin And Lysozyme To Promote Nutritional, Clinical And Enteric Recovery: A Protocol For A Factorial, Blinded, Placebo-Controlled Randomised Trial Among Children With Diarrhoea And Malnutrition (The Boresha Afya Trial), Ruchi Tiwari, Kirkby Tickell, Emily Yoshioka, Joyce Otieno, Adeel Shah, Barbra Richardson, Lucia Keter, Maureen Okello, Churchil Nyabinda, Indi Trehan

Paediatrics and Child Health, East Africa

Introduction: Children with moderate or severe wasting are at particularly high risk of recurrent or persistent diarrhoea, nutritional deterioration and death following a diarrhoeal episode. Lactoferrin and lysozyme are nutritional supplements that may reduce the risk of recurrent diarrhoeal episodes and accelerate nutritional recovery by treating or preventing underlying enteric infections and/or improving enteric function.

Methods and analysis: In this factorial, blinded, placebo-controlled randomised trial, we aim to determine the efficacy of lactoferrin and lysozyme supplementation in decreasing diarrhoea incidence and improving nutritional recovery in Kenyan children convalescing from comorbid diarrhoea and wasting. Six hundred children aged 6–24 months with …

Uncovering The Hidden Diversity Of Antibody Heavy Chains And Their Implications For Autoantibody Mediated Disease., Easton Earl Ford

Electronic Theses and Dissertations

Understanding the diversity of antibody (IG) molecules at the DNA and RNA level is imperative for understanding immunological processes and disease. Much of the work to uncover IG diversity has been focused on diversity in the variable region of the IG molecule which is crucial for antigen binding. However, the diversity of the constant region responsible for the functions of IG has largely been ignored in the field of immunogenetics. The work presented in this thesis challenges the dogma that the constant region is invariant in terms of genetic diversity. In this thesis we present the development of a long-read …

Partial Immunity To Mycoplasma Gallisepticum After An Initial Infection Is Long-Lasting And Reduces Transmission In Flocks Of Canaries, Madeline Sudnick

Graduate Theses and Dissertations

Pathology during a second infection can be influenced by immunity and an increase in resistance or tolerance of individuals. Population-level differences in the ability to maintain immunity can lead to contrasting survival outcomes between groups and determine how future outbreaks will spread. However, long term wildlife disease surveillance can be challenging due to lack of infrastructure and host-pathogen specific tests. Calculating disease transmission likelihood requires understanding individual-level heterogeneity in pathology and behavior, and there is limited knowledge in understanding how populations in different stages of an epidemic will transmit disease. In Chapter I, we aim to help fill a gap …

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, …

The Role Of Micrornas On Systemic And Central Nervous System- Inflammation In Aged Mice, Anik Banerjee

Dissertations and Theses (Open Access)

MicroRNAs play a crucial role in multiple biological processes, including development, cell differentiation, proliferation, metabolism, and cell death. Aberrant regulation of microRNAs is seen in many diseases, such as sepsis, cardiovascular disease, neurological diseases such as stroke, and metabolic disorders. Because of their involvement in disease processes, microRNAs have been investigated as both potential biomarkers, and as therapeutic targets. Age-related inflammatory diseases including diabetes, obesity, and atherosclerosis are important risk factors for infection and sepsis. Intestinal barrier impairment occurs with aging and after brain injuries, including stroke. Both aging and stroke increase the risk of infection and sepsis and are …

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 …

Omani Camels From A Cultural And Genomics Perspective, Al Muatasim Al Zadjali

Electronic Theses and Dissertations

The Dromedarian camel, Camelus dromedarius, is native to the Arabian Peninsula, including the Sultanate of Oman. These camels are used for food, milk, as well as show and racing competitions. Despite their economic and cultural importance research on camels in Oman is limited. The goal of this study was to examine their genomic variation, relationship with camels in other parts of the Arabian Peninsula, and to determine if selective breeding has led to the establishment of distinct breeds in Oman. Information was compiled from multiple sources to produce a comprehensive review on the breeding, management, economic and cultural use, …

Therapeutic Effects Of Bet Protein Inhibition In B-Cell Malignancies And Beyond, Audrey L. Smith

Theses & Dissertations

Chronic lymphocytic leukemia (CLL) develops through a combination of intrinsic genetic defects, constitutively active survival/proliferation signaling pathways, and complex microenvironment interactions. Redundant tumor microenvironment (TME) immuno-suppressive mechanisms and epigenetic maintenance of terminal T-cell dysfunction also greatly hinder anti-tumor T-cell responses in CLL. Small-molecule agents targeting the B-cell receptor (BCR) pathway and anti-apoptotic proteins alone or in combination with chemo-immunotherapy have revolutionized the management of CLL, yet there is still a significant need for novel therapeutic strategies to yield durable tumor elimination. Bromodomain and extra-terminal domain (BET) proteins are epigenetic readers that bind to acetyl-lysine residues on histones to regulate gene …

The Role Of B Cell Activation State And Sex In Aryl Hydrocarbon Receptor Mediated Induction Of Chemokine Receptor 9 And Alpha4beta7 Expression In Vitro, Logan Bauerle

Master's Theses

Defense of mucosal tissues from microbial infection and allergy is reliant on continual production of antibodies. The aryl hydrocarbon receptor (AhR) is known to regulate B cell development and is associated with suppression of systemic humoral immunity. Recent attention has been paid to the role of the AhR in altering expression of cell adhesion molecules (CAMs). B cells express CAMs and chemokine receptors to migrate around the body for localized secretion of antibodies. AhR agonists promote B cell migration to the small intestine through upregulation of chemokine receptor 9 (CCR9) and integrin α₄β₇. Both the AhR …