Immunology of Infectious Disease Commons^™

Using Rainbow Trout Cell Lines As A Model For Understanding The Innate Anti-Fv3 Immune Response, Graeme Robert Jones Lisser

Theses and Dissertations (Comprehensive)

Ranavirus infections are on the rise and have been implicated in numerous species die-offs across the globe. Frog virus 3 (FV3) is the type-species of the genus, yet the immune mechanisms governing susceptibility remain poorly understood. Arguably the most important immune response to infection is the type I interferon (IFN) response. Type I IFNs trigger an “antiviral state” in host cells via the production of numerous interferon-stimulated genes (ISGs) that act to inhibit virus replication in various way, including the induction of apoptosis. Apoptosis is an important antiviral defense mechanism to limit virus replication within infected cells. This study employed …

Regulation Of Alpha-Herpesvirus Reactivation From Latency By Stress, Insun Kook

School of Veterinary and Biomedical Sciences: Dissertations, Theses, and Student Research

Bovine herpes virus 1 (BHV-1) and Herpes simplex virus 1 (HSV-1) are crucial etiological viral agent of clinical diseases. HSV-1 and BHV-1 establish latent infection in sensory neurons. Periodically, reactivation from latency occurs resulting in virus excretion and transmission. Stress increases corticosteroid levels and the incidence of HSV-1 and BHV-1 reactivation from latency. The synthetic corticosteroid, dexamethasone (DEX) mimics stress and induces BHV-1 and HSV-1 reactivation. However, molecular mechanisms by which corticosteroid mediates viral reactivation are not well understood. My dissertation has focused on elucidating events that induce BHV- 1 or HSV-1 reactivation during the early stages of stress-induced escape …

Nucleoside-Diphosphate-Kinase Of P. Gingivalis Is Secreted From Epithelial Cells In The Absence Of A Leader Sequence Through A Pannexin-1 Interactome, Kalina Atanasova, Jungnam Lee, Joann Roberts, Kyulim Lee, David M. Ojcius, Özlem Yilmaz

All Dugoni School of Dentistry Faculty Articles

Nucleoside-diphosphate-kinases (NDKs) are leaderless, multifunctional enzymes. The mode(s) of NDK secretion is currently undefined, while extracellular translocation of bacterial NDKs is critical for avoidance of host pathogen clearance by opportunistic pathogens such as Porphyromonas gingivalis. P. gingivalis-NDK during infection inhibits extracellular-ATP (eATP)/P2X7-receptor mediated cell death in gingival epithelial cells (GECs) via eATP hydrolysis. Furthermore, depletion of pannexin-1-hemichannel (PNX1) coupled with P2X7-receptor blocks the infection-induced eATP release in GECs, and P. gingivalis-NDK impacts this pathway. Ultrastructural and confocal microscopy of P. gingivalis-co-cultured GECs or green-fluorescent-protein (GFP)-P. gingivalis-NDK transfected GECs revealed a perinuclear/cytoplasmic localization of NDK. eATP stimulation induced NDK recruitment to …

An Iron Detection System Determines Bacterial Swarming Initiation And Biofilm Formation, Chuan-Sheng Lin, Yu-Huan Tsai, Chih-Jung Chang, Shun-Fu Tseng, Tseng-Ru Wu, Chia-Chen Lu, Ting-Shu Wu, Jang-Jih Lu, Jim-Tong Horng, Jan Martel, David M. Ojcius, Hsin-Chih Lai, John Ding-E. Young

All Dugoni School of Dentistry Faculty Articles

Iron availability affects swarming and biofilm formation in various bacterial species. However, how bacteria sense iron and coordinate swarming and biofilm formation remains unclear. Using Serratia marcescens as a model organism, we identify here a stage-specific iron-regulatory machinery comprising a two-component system (TCS) and the TCS-regulated iron chelator 2-isocyano-6,7-dihydroxycoumarin (ICDH-Coumarin) that directly senses and modulates environmental ferric iron (Fe3+) availability to determine swarming initiation and biofilm formation. We demonstrate that the two-component system RssA-RssB (RssAB) directly senses environmental ferric iron (Fe³⁺) and transcriptionally modulates biosynthesis of flagella and the iron chelator ICDH-Coumarin whose production requires the pvc cluster. …

Novel Mutation Of Interferon-Γ Receptor 1 Gene Presenting As Early Life Mycobacterial Bronchial Disease, Maria J. Gutierrez, Neelu Kaira, Alexandra Horwitz, Gustavo Nino

Pediatrics Faculty Publications

Mendelian susceptibility to mycobacterial diseases (MSMD) are a spectrum of inherited disorders characterized by localized or disseminated infections caused by atypical mycobacteria. Interferon-γ receptor 1 (IFNGR1) deficiency was the first identified genetic disorder recognized as MSMD. Mutations in the genes encoding IFNGR1 can be recessive or dominant and cause complete or partial receptor deficiency. We present the case of a 2½-year-old boy with a history of recurrent wheezing, diagnosed with endobronchial mycobacterial infection. Immunological workup revealed a homozygous nonsense mutation in the IFNGR1 gene, a novel mutation predicted in silico to cause complete IFNGR1 deficiency. This case demonstrates that ( …

Pyk2 Activates The Nlrp3 Inflammasome By Directly Phosphorylating Asc And Contributes To Inflammasome-Dependent Peritonitis, I-Che Chung, Chun-Nan Ouyang, Sheng-Ning Yuan, Hsin-Pai P. Li, Jeng-Ting Chen, Hui-Ru Shieh, Yu-Jen Chen, David M. Ojcius, Ching-Liang Chu, Jau-Song Yu, Yu-Sun Chang, Lih-Chyang Chen

All Dugoni School of Dentistry Faculty Articles

The inflammasome adaptor protein, ASC, contributes to both innate immune responses and inflammatory diseases via self-oligomerization, which leads to the activation of the protease, caspase-1. Here, we report that the cytosolic tyrosine kinases, FAK and Pyk2, are differentially involved in NLRP3 and AIM2 inflammasome activation. The inhibition of FAK and Pyk2 with RNA interference or chemical inhibitors dramatically abolished ASC oligomerization, caspase-1 activation, and IL-1β secretion in response to NLRP3 or AIM2 stimulation. Pyk2 is phosphorylated by the kinase Syk and relocalizes to the ASC specks upon NLRP3 inflammasome activation. Pyk2, but not FAK, could directly phosphorylate ASC at Tyr146, …

Modeling Cross-Species Extrapolation Of Inhalation Anthrax For Risk Assessment Purposes, Megan O. Powell

Annual Symposium on Biomathematics and Ecology Education and Research

No abstract provided.

Utilization Of Cholera Toxin B As An Adjuvant For The Subunit Pspa Vaccine, Provides Effective Protection Against Streptococcus Pneumoniae Challenge, Daniel R. Pinho

Seton Hall University Dissertations and Theses (ETDs)

Streptococcus pneumoniae is a prevalent human pathogen associated with pneumonia. It is estimated that approximately 1 million people around the world die each year, specifically with young children and the elderly comprising a significant portion. Currently, antibiotics can treat the infection but individuals such as the young or elderly are more susceptible to bodily damage from symptoms, such as pneumonia, meningitis, and sepsis, thus require more preventive measures. As a result, vaccinations are a key solution to providing effective protection against infectious pathogens. Presently, two vaccinations exist in the market: PPSV₂₃ and PCV₁₃, which only protect against …

Cannabinoids Suppress The Innate Immune Response To Periodontal Pathogen Porphyromonas Gingivalis In Gingival Epithelial Cells., Rajarshi Guha Niyogi

Electronic Theses and Dissertations

Marijuana is widely used in the United States for recreational and medicinal purposes. Despite the proposed beneficial effects of cannabis on certain medical conditions, there is also a concern there is also a concern over negative health consequences of marijuana smoking. Recently, cannabis use has been established as a dose related risk factor for chronic periodontitis. Although the induction / exacerbation of chronic periodontitis in marijuana users has been established epidemiologically, the mechanisms underlying such predisposition are still unknown. It has long been suggested that marijuana has anti-inflammatory properties, while human epithelial cells are known to express cannabinoid receptor type …

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 …

Identification Of Biomarkers Associated With Rous Sarcoma Virus-Induced Tumors In Two Divergently Selected Chicken Lines, Ashley Hayden

Graduate Theses and Dissertations

Poultry has become especially important to genetic research due to breeding feasibility, short generation turnover, and ease of maintaining large populations. The discovery of virus induced cancer has paved the way for further genetic studies. Rous Sarcoma Virus (RSV) is a tumor-causing virus that infects poultry. While not prevalent today, it can serve as a model for virus-induced cancer in humans and create additional insight to marker assisted selection in poultry. Genetically selected Arkansas Progressor (AP) and Arkansas Regressor (AR) chicken lines have been established and maintained at the Arkansas Experimental Station (AES) in Fayetteville, AR. Previous research has investigated …

Innate Immunity In Chickens: In Vivo Responses To Different Pathogen Associated Molecular Patterns, Kristen Alicia Byrne

Graduate Theses and Dissertations

Pattern recognition receptors (PRRs) on host cells recognize motifs known as pathogen associated molecular patterns (PAMPs) that are common to groups of microbes. Examples include LPS on Gram-negative bacteria, the structural motif PGN common to all bacteria, MDP the smallest immunostimulatory unit of PGN, and poly I:C the dsRNA analog. PAMP recognition by and stimulation of the innate immune system is crucial to an individual’s ability to quickly limit microbial growth and stimulate the adaptive immune system. Characterization of the in vivo immune responses initiated by PAMPs has not been directly addressed. Using growing feathers (GF) as a novel intradermal …

Hepatitis C Virus Frameshift/Alternate Reading Frame Protein Suppresses Interferon Responses Mediated By Pattern Recognition Receptor Retinoic-Acid-Inducible Gene-I, Seung Bum Park, Scott Seronello, Wasima Mayer, David M. Ojcius

All Dugoni School of Dentistry Faculty Articles

Hepatitis C virus (HCV) actively evades host interferon (IFN) responses but the mechanisms of how it does so are not completely understood. In this study, we present evidence for an HCV factor that contributes to the suppression of retinoic-acid-inducible gene-I (RIG-I)-mediated IFN induction. Expression of frameshift/alternate reading frame protein (F/ARFP) from HCV -2/+1 frame in Huh7 hepatoma cells suppressed type I IFN responses stimulated by HCV RNA pathogen-associated molecular pattern (PAMP) and poly(IC). The suppression occurred independently of other HCV factors; and activation of interferon stimulated genes, TNFα, IFN-λ1, and IFN-λ2/3 was likewise suppressed by HCV F/ARFP. Point mutations in …

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 …

Mathematical Models Of Hiv And Hpv Coinfection, Samantha Erwin, Meghna Verma, Vida Abedi, Raquel Hontecillas-Magarzo, Stefan Hoops, Josep Bassaganya-Riera, Stanca M. Ciupe

Biology and Medicine Through Mathematics Conference

No abstract provided.

Needle In The Haystack: Combining Intravital Imaging And Mathematical Modeling To Understand How Vaccine-Induced T Cells Find Malaria-Infected Cells In Murine Livers, Vitaly V. Ganusov, Ian Cockburn, Reka Kelemen

Biology and Medicine Through Mathematics Conference

No abstract provided.

Hiv Vaccines: Progress, Limitations And A Crispr/Cas9 Vaccine, Omar A. Garcia Martinez

Biology: Student Scholarship & Creative Works

ABSTRACT: The HIV-1 pandemic continues to thrive due to ineffective HIV-1 vaccines. Historically, the world’s most infectious diseases, such as polio and smallpox, have been eradicated or have come close to eradication due to the advent of effective vaccines. Highly active antiretroviral therapy is able to delay the onset of AIDS but can neither rid the body of HIV-1 proviral DNA nor prevent further transmission. A prophylactic vaccine that prevents the various mechanisms HIV-1 has to evade and attack our immune system is needed to end the HIV-1 pandemic. Recent advances in engineered nuclease systems, like the CRISPR/Cas9 system, have …

Norovirus Infection And Acquired Immunity In 8 Countries: Results From The Mal-Ed Study, Furqan Kabir, Adil Kalam, Pascal Bessong Pascal Bessong, Zulfiqar Ahmed Bhutta, Anita K. M. Zaidi, (Mal-Ed) Network Investigators, Imran Ahmed, Didar Alam, Syed Asad Ali, Shahida Qureshi, Muneera Rasheed, Sajid Bashir Soofi, Ali Turab, Aisha Khizar Yousafzai

Department of Paediatrics and Child Health

Background: Norovirus is an important cause of childhood diarrhea. We present data from a longitudinal, multicountry study describing norovirus epidemiology during the first 2 years of life.
Methods: A birth cohort of 1457 children across 8 countries contributed 7077 diarrheal stools for norovirus testing. A subset of 199 children contributed additional asymptomatic samples (2307) and diarrheal stools (770), which were used to derive incidence rates and evaluate evidence for acquired immunity.
Results: Across sites, 89% of children experienced at least 1 norovirus infection before 24 months, and 22.7% of all diarrheal stools were norovirus positive. Severity of norovirus-positive diarrhea was …

Synthesis And Evaluation Of Biological Activity Of A Potential Immunomodulatory Zwitterionic Polysaccharide, Vikram Basava

Seton Hall University Dissertations and Theses (ETDs)

The gram-negative anaerobic bacterium Bacteroides fragilis is an integral component of the normal gastrointestinal flora. The bacterium colonizes the intestinal tract of human beings as it has no reservoir other than mammals. An unprecedented proportion of the genomic DNA of B. fragilus is involved in the production of capsular polysaccharides. These capsular polysaccharides are important virulence factors in most extracellular bacterial pathogens. Eight of these polysaccharides have been identified thus far, out of which two were found to be zwitterionic polymers, PSA1 and PSA2. PSA1 was found to stimulate T-cell lineage of the immune system because of the dual charge …

Comparison Of Anti-Pneumococcal Functions Of Native And Modified Forms Of C-Reactive Protein, Donald Neba Ngwa

Electronic Theses and Dissertations

The anti-pneumococcal function of native C-reactive protein (CRP) involves its binding to phosphocholine molecules present on Streptococcus pneumoniae and subsequent activation of the complement system. However, when pneumococci recruit complement inhibitory protein factor H on their surface, they escape complement attack. Non-native forms of CRP have been shown to bind immobilized factor H. Accordingly, we hypothesized that modified CRP would bind to factor H on pneumococci, masking its complement inhibitory activity, allowing native CRP to exert its anti-pneumococcal function. As reported previously, native CRP protected mice from lethal pneumococcal infection when injected 30 minutes before infection but not when injected …