Life Sciences Commons^™

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

MSU Graduate Theses

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 …

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

MSU Graduate Theses

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 …

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

MSU Graduate Theses

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 …

Influence Of Cell Cycle On Aim2 Inflammasome Activation, Ashok Kumar Dubey

MSU Graduate Theses

A cell cycle's progression has a significant role in the development of a disease. All the signaling pathways and inflammatory reactions are maintained in a healthy mode if cell cycle checkpoints are precisely regulated and kept in homeostasis. AIM2 inflammasome is a cytoplasmic double-stranded DNA sensor. Upon activation, it elicits an inflammatory reaction with the release of pro-inflammatory cytokines such as IL-1β and IL-18 and they are cleaved by the proteases, Caspase-1 from their inactive form. Also, the AIM2 inflammasome helps in regulating cell division and inhibits cell proliferation; thus, leading to a cell death called pyroptosis. Here, I examined …

The Comparison Of Three Different Fecal Egg Counting Techniques And Their Ability To Perform A Fecal Egg Count Reduction Test, Diana J. Summitt

MSU Graduate Theses

A comprehensive gastrointestinal parasite control program includes an understanding of common parasites, application of chemotherapeutic agents, as well as frequent and appropriate diagnostic testing. An effective control program is essential for facilities such as animal shelters, that deal with large populations of transient canines with unknown parasite exposure and deworming history. The identification of a sensitive flotation method to evaluate anthelmintic efficacy is critical in monitoring parasite populations for drug resistance. The objective of the current study was to compare three different fecal egg counting technologies and their ability to perform a fecal egg reduction test. The flotation techniques evaluated …

Identification Of A Novel Protein Interaction That Elucidates The Mechanism Of Idiopathic Recurrent Miscarriages In Women With Nlrp2 Mutations, Nayeon Son

MSU Graduate Theses

The protein NOD-Like receptor pyrin domain containing 2 (NLRP2) is one member of a larger family of protein receptors that plays an important role in our innate immune system. In humans, the NLR family consists of 22 proteins. However, only about a half of NLRs’ functions are known, but many are pro-inflammatory, causing inflammation. NLRP2 has been identified to be a maternal effect gene regulating early embryo development in idiopathic recurrent miscarriages. In previous studies, mutations in the NLRP2 gene resulted in genetic maternal imprinting disorders due to NLRP2 regulating DNA methylation. However, the exact mechanisms involved in recurrent miscarriages …

Effects Of Natural Products On Inflammation, Riley Ann Nadler

MSU Graduate Theses

Chronic inflammation is characterized by infiltration of inflammatory cells such as macrophages and lymphocytes into the tissue where they produce inflammatory cytokines that contribute to tissue damage. Worldwide, 3 out of 5 people die due to chronic inflammatory diseases like cardiovascular diseases, obesity, diabetes, and cancer. Since it is well-documented that diet and metabolism are key mediators of inflammation, I investigated the effects of dietary lectins on inflammatory cytokine production and the ability of sodium pyruvate, a metabolite, to decrease inflammation. In chapter 1, I examined the effect that lectins from either Triticum vulgaris (common wheat) or Phaseolus vulgaris (common …

The Role Of The Host Factor Sptbn1 In Hiv-1 Infection Of Microglial Cells, Marc Gordon Havlicek

MSU Graduate Theses

HIV-1 is the etiological agent that cause AIDS. Since the 1980’s when HIV-1 was discovered, much has been discovered, however a cure for HIV-1 has eluded researchers. Effective therapeutics do exist but can have adverse side effects including HAND/HAD which leads to neurodegeneration in patients regardless of viral suppression. One area of research that holds the possibility of discovering new viral targets and therapeutics is host factor interaction within the replication process. One host factor that can cause a decrease in HIV-1 infectivity is SPTBN1. SPTBN1 is a cytoskeletal protein that was shown to bind to the capsid and nucleocapsid …

Nucleotide P2y₂ Receptor-Dependent Leukocyte-Endothelial Interaction, Spencer E. Thomas

MSU Graduate Theses

Extracellular nucleotides (ATP, UTP) released from cells act on nucleotide receptors to promote vascular inflammation. Increased leukocyte-endothelial interaction is a hallmark of vascular inflammation. The nucleotide P2Y₂ receptor (P2Y₂R), activated by extracellular ATP≈UTP, plays a role in cardiovascular homeostasis and immune regulation. Moreover, accumulating evidence from studies in vitro and in vivo models have implicated the P2Y₂R in the inflammatory response significantly contributing to the progression and pathogenesis of asthma, atherosclerosis, sepsis, and ischemia. I hypothesized that P2Y₂R activation by UTP, an agonist of the receptor, increased leukocyte rolling and adhesion in the microvasculature from baseline. To test the hypothesis, …

Sodium Pyruvate Ameliorates Influenza A Virus Infection In Vitro And In Vivo, Jessica M. Reel

MSU Graduate Theses

Pyruvate is produced in duplicate at the end of glycolysis in addition to ATP and NADH. Pyruvate is the metabolite of choice in most cells, whether obtained exogenously or endogenously. Recently we found that the addition of pyruvate’s conjugate base, sodium pyruvate, to cell culture media dampened the immune response to influenza A virus (IAV) infection in cultured innate immune cells. Thus, I decided to investigate the mechanism and potential for treatment of IAV. In vitro using bone marrow derived macrophages that were infected with IAV we found that adding sodium pyruvate to the media decreased immune signaling pathways through …

Elucidating Immune Signaling Of Influenza A Virus And Aspergillus Fumigatus Co-Infections Through Pioneered Model Development, Meagan Danyelle Rippee-Brooks

MSU Graduate Theses

Bacterial co-infections with influenza A virus (IAV) are extremely serious and life-threatening. However, there exists limited understanding about the importance of fungal infections with IAV. Clinical case reports indicate that fungal co-infections do occur and suggest the IAV pandemic of 2009 had a propensity to predispose patients to secondary fungal infections more than previous IAV strains. IAV-fungal co-infections are marked by high mortality rates of 47 to 61% in previously healthy individuals between the ages of 20 and 60. Yet, the variables involved in this co-infection remain undetermined. I achieved effective recapitulation of this co-infection using a C57Bl/6 murine (mouse) …

An Examination Of The Potential Threat Of A State-Sponsored Biological Attack Against The United States: A Study Of Policy Implications, Courtney Anne Pfluke

MSU Graduate Theses

In 2002, US Navy Seals found a list of pathogens in an Afghanistan cave that Al Qaeda had planned to use in a series of biological attacks. Unique about the discovery was that the pathogens were not limited to human ones. Six pathogens targeted livestock and four targeted crops. Despite this discovery, limited attention has been given to the possibility of a state-sponsored terrorist attack utilizing biological agents against the US population, food source, or water supply. Throughout history, biological agents have been developed for use as an offensive weapon for both states and terrorist groups. The United States may …

White-Nose Syndrome And Immune Responses In A Resistant Bat Species (Eptesicus Fuscus), Keslie Skye Naffa

MSU Graduate Theses

White-nose syndrome (WNS) has had a large negative impact on bat populations across eastern North America since its arrival in 2006. Bats affected by WNS appear to die of starvation, possibly due to the increased arousals during hibernation when there is no food present to replace the energy used to arouse. During hibernation, the bat’s immune system should be suppressed. However, once a bat of a susceptible species is exposed to the fungus that causes WNS, Psuedogymnoascus destructans (Pd), the immune system seems to respond, potentially causing an elevation in metabolic rate, which may cause the bat to …

Immune Function And Metabolism Of Hibernating North American Bats With White-Nose Syndrome, Briana Nicole Anderson

MSU Graduate Theses

White-nose syndrome (WNS) causes substantial mortality in certain species of hibernating North American bats. The responsible agent is Pseudogymnoascus destructans (Pd), a fungus which causes physiological complications such as increased arousals and energy depletion during the hibernation season. Tricolored bats (Perimyotis subflavus) and northern long-eared bats (Myotis septentrionalis) suffer extensive WNS mortality, while gray bats (Myotis grisescens) and big brown bats (Eptesicus fuscus) are infected, but mortality is rarely observed. It is hypothesized that there is a difference in immune responses and/or hibernation metabolism between these bat species, resulting in this …

Sodium Pyruvate Alters The Immune Response To Influenza A Virus Infection In Macrophages, Hazzar Abysalamah

MSU Graduate Theses

ABSTRACT

Pyruvate is the end product of glycolysis. It can either be transported into the mitochondria for use in the TCA cycle or be used to regenerate NAD⁺ during fermentation or aerobic glycolysis (also called the Warburg Effect). I recently discovered that addition of sodium pyruvate to the culture medium during infection of macrophages with influenza A virus affects the production of cytokines involved in immune signaling. While infection of macrophages with influenza A virus resulted in high levels of cytokines (IL-6, IL-1β, and TNF-α) in the absence of sodium pyruvate, the addition of sodium pyruvate significantly impaired cytokine …

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

MSU Graduate Theses

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