Immunology and Infectious Disease Commons^™

No Effect In Plasma Corticosterone Levels After Observation Of Diseased Conspecifics, B. M. Hardy, M. Chang, S. Mccallum, S. Santangelo, Patricia C. Lopes

Biology, Chemistry, and Environmental Sciences Faculty Articles and Research

Organisms commonly respond to stressors in their environment by increasing the secretion of corticosterone (CORT). While increased CORT is acknowledged as a response to predation risk by organisms inhabiting a landscape of fear, new research raises the potential for changes in CORT as a response to the risk of infection by organisms in their environment. An increase in CORT of a healthy, uninfected individual in response to their perception of the risk of infection in their environment could change their susceptibility to infection, highlighting a significant role for CORT to alter host–pathogen dynamics. To investigate the effects of infection risk …

Evaluation Of Il-10 And Il-12 As Early Diagnostic Biomarkers In Type 2 Diabetes Mellitus, Mariam Sami Shail, Israa Hussein Hamzah

Maaen Journal for Medical Sciences

Background: Type 2 diabetes mellitus (T2DM) is increasingly recognized as a complex metabolic disorder associated with immune dysregulation and chronic low-grade inflammation Objectives: This study aimed to quantify serum levels of (IL-10) and (IL-12) in patients with (T2DM) and to explore their potential role as early diagnostic biomarkers in comparison with healthy controls. Methods:  A case–control study be situated showed including 120 participants: 80 patients with T2DM and 40 healthy controls. Serum concentrations of IL-10 and IL-12 were quantified using ELISA. Hematological and biochemical parameters were assessed using standard automated methods. Statistical analyses included independent t-tests, correlation analysis, and receiver …

Targeting Cancer With T Cells: Preclinical And In Silico Insights To Improve Immunotherapies, Nina Obertopp

USF Tampa Graduate Theses and Dissertations

T-cell–based immunotherapies are often constrained by limited trafficking and persistence in tumors and by functional exhaustion under chronic antigen exposure. This dissertation addresses these barriers through two distinct strategies: (i) preclinical studies testing how radiation therapy modulates tumor-infiltrating lymphocytes (TIL) therapy, and (ii) agent based modeling (ABM) to optimize treatment day treatment-free intervals (TFI) in T-cell engager (TCE) therapy. (i) In a human papillomavirus–positive (HPV⁺) head-and-neck cancer (HNC) model, a single local-dose of RT (8 Gy) delivered five days before tumor harvest increased the success and functional quality of ex vivo TIL outgrowth from tumor fragments, enriching polyfunctional CD8⁺ subsets. …

Fisheries Occasional Publication No. 150 - Response To 2024 External Review Of Integrated Stock Assessments For Key Wa Demersal Indicator Stocks, Rubie Evans-Powell, S. A. Hesp, Ainslie Denham, Emily A. Fisher, Rachel Marks, Fabian I. Trinnie, Brett Crisafulli

Fisheries Occasional Publications

In Western Australia (WA), stock assessments for key demersal species, including snapper and red emperor, have traditionally used bespoke integrated models developed in-house by the Department of Primary Industries and Regional Development (DPIRD). In line with other Australian jurisdictions, DPIRD is transitioning to Stock Synthesis (SS) as its primary platform for integrated stock assessments of WA finfish. To support this transition, DPIRD commissioned an independent expert review of recent integrated models applied to three demersal stocks. This publication responds to recommendations from Professor André Punt (University of Washington and CSIRO) in his 2024 review, which examined assessments for Pilbara red …

Cytotoxic And Antimicrobial Effects Of Plant-Derived Compounds Used In Traditional Chinese Medicine, Amanda Ly, Diane Sun, Shelbi Salinas, Victor M. Jimenez

Annual Research Symposium

No abstract provided.

Mycobacteria Infection Induced Cascade Of Epigenetic Alterations Promote Training In Bystander Macrophages, Shah E. Jahan Gulzar Mr

Theses and Dissertations

Mycobacterium tuberculosis (Mtb) remodels host cell functions to support its intracellular persistence. While the effects of Mtb infection on infected macrophages are well characterized, responses of uninfected bystander cells in the same microenvironment remain poorly understood. Here, we show that Mtb infection triggers widespread epigenetic reprogramming not only in infected macrophages but also in neighbouring bystander cells. These bystander macrophages acquire active chromatin marks, exhibit distinct transcriptional changes, and display enhanced immune responsiveness, thereby increasing resistance to both homologous and heterologous infections. We identify interleukin-1 beta secreted by infected cells as a key mediator of this process. Functionally, trained bystander …

Gene Regulatory Programs Of Nk Cells Show That Ncam1 (Cd56) And Kirs Are Controlled By Genetically Polymorphic Distal Regulatory Elements, Mariam A. Salem, Aditi Varkey, Matthew D. Estrada, Kruthika Sharma, Caprice D. Eisele, Nitin Chakravarti, Dean A. Lee, Aharon G. Freud, Bethany L. Mundy-Bosse, Patrick L. Collins

Kimmel Cancer Center Faculty Papers

Owing to their immunoprotective properties, natural killer (NK) cells are critical for the innate immune response to pathogens, as well as a new wave of cancer immunotherapy that harnesses natural cytotoxicity. We sought to study the genetic and epigenetic drivers behind human-specific NK cell receptors, so that we can better understand the underlying cellular function. Here, we present a transcriptomic, proteomic (CITE-seq), and chromatin (single nuclei ATAC-seq) profiling of human peripheral NK cell subsets, which was then compared with genomic databases. Through integrative multi-omics, we demonstrate that CD56^bright versus CD56^dim NK cell subsets have differential distal regulatory element …

Immunogenicity And Efficacy Of A Rabies-Based Vaccine Against Highly Pathogenic Influenza H5n1 Virus, Nir Paran, Christoph Wirblich, Randy Albrecht, Leila Zabihi Diba, Alessandro Tarquinio, Drishya Kurup, Charalambos C. Solomides, Adolfo García-Sastre, Matthias J. Schnell

Department of Microbiology and Immunology Faculty Papers

The recent spillover of highly pathogenic influenza A/H5N1 (HPAI-H5N1) viruses to cattle, other mammals, and humans poses a major risk to animal and human health. Virus adaptation to new species highlights the need for effective vaccines for animals and humans. We recently developed a rabies virus-based H5 vaccine encoding the HPAI-H5 antigen and presenting it on the surface of the rabies virus particle. To test the immunogenicity and efficacy of the vaccine in eliciting systemic and mucosal immune response, we vaccinated mice intramuscularly or intranasally with either live or inactivated and adjuvanted vaccine. The vaccine elicited neutralizing antibodies against RABV …

Combined Glycoprotein Mutations In Rabies Virus Promote Astrocyte Tropism And Protective Cns Immunity In Mice, Mirjam Anna Rita Bertoune, Corinna Kolbe, Ann-Cathrin Werner, Maren Steinmetz, Bernhard Dietzschold, Eberhard Weihe

Department of Microbiology and Immunology Faculty Papers

Rabies virus (RABV) causes fatal encephalitis once it invades the central nervous system (CNS), and treatment options are extremely limited at this stage. We investigated the recombinant RABV variants SPBN, SPBNGA (glycoprotein substitution R333E), SPBNGAK (R333E plus N194K), SPBNGAS (R333E plus N194S), and TriGAS (three copies of the R333E/N194S glycoprotein). We evaluated their cellular tropism and immune activation in an intracerebral mouse infection model using immunohistochemistry and confocal immunofluorescence. SPBNGAK (R333E/N194K) resulted in mixed neuronal and astrocytic infection and lethal disease. In contrast, the R333E/N194S mutations in the GAS variants were associated with reduced neuronal infection and apparent astrocyte-restricted infection …

Phase 1b/2 Study Of Bms-813160, A Ccr2/5 Dual Antagonist, In Combination With Chemotherapy Or Nivolumab In Patients With Advanced Pancreatic Or Colorectal Cancer, Dung T. Le, Gunnar Folprecht, Anna M. Varghese, Martin Gutierrez, Marcus Noel, Nikolaos A. Trikalinos, Eric Chen, Farshid Dayyani, S. Lindsey Davis, Wen Wee Ma, Atrayee Basu Mallick, Ignacio Garrido-Laguna, Mayu Osawa, Shaun O'Brien, Ruslan D. Novosiadly, Ke Xu, Danielle M. Greenawalt, Santanu Dutta, Christina Twyman Saint Victor, Heinz-Josef Lenz

Department of Medical Oncology Faculty Papers

BACKGROUND: Cysteine-cysteine chemokine receptors 2 (CCR2) and 5 (CCR5) contribute to immune suppression in tumor microenvironments. CCR2 and CCR5 antagonists have demonstrated antitumor activity in pancreatic ductal adenocarcinoma (PDAC) and colorectal cancer (CRC), respectively. This phase 1b/2, open-label study evaluated BMS-813160, a CCR2/5 dual antagonist, in combination with chemotherapy±nivolumab in advanced PDAC or metastatic CRC.

METHODS: Part 1 included patients with metastatic untreated (first-line (1L)) PDAC, 1L CRC, or previously treated (second or third line (2/3L)) microsatellite stable (MSS) CRC. Patients received 2 weeks of BMS-813160 monotherapy (300 mg two times a day, 600 mg once daily, 300 mg once …

Contribution To The Chemotherapy Of Human Trypanosomiasis: Design, Synthesis, And Biological Evaluation Of Dimeric 2-Nitroimidazoles Against Trypanosoma Cruzi Amastigotes And Bloodstream Trypanosoma Brucei, Afonso Santine M.M. Velez, Otavio Augusto Chaves, Carlos Serpa, Fatma M. Salem, Bibo Li Ph.D., Bin Su Ph.D., Celio Geraldo Freire-De-Lima, Debra Decote-Ricardo, Marco Edilson Freire De Lima

Biological, Geological, and Environmental Faculty Publications

Effective and safe treatments for neglected tropical diseases caused by parasites, such as Chagas disease and sleeping sickness, remain lacking, posing a significant challenge for researchers worldwide. The rational design of dimeric compounds inspired solely by the pharmacophoric core of benznidazole (2-nitroimidazole) has proven to be a promising strategy for antiparasitic development. Thus, in the present work, it was increased the linker between the active units (2-nitroimidazole) to improve the interaction with TcNTR, facilitating the bioactivation of the longest dimers. Biological assays confirmed this, demonstrating that all compounds were active against replicative intracellular amastigotes of Trypanosoma cruzi (Tulahuen C2C4-LacZ). Notably, …

A Probabilistic Modeling Analysis Of The Longitudinal Immune Response To Infection And Vaccination Across Demographic Groups And Pulmonary Symptoms, James O'Hanlon, Kaitlyn Sullivan, Lyndsey M. Muehling, Glenda Canderan, Jie Sun, Judith A. Woodfolk, Jeffrey M. Wilson, Rayanne A. Luke

Spora: A Journal of Biomathematics

Antibody and cytokine kinetics describe the dynamic response to immune events such as infection and vaccination. These dynamics are not fully understood, and mathematical characterization may help explain variability across demographic groups and pulmonary symptoms post-acute infection. We fit time-dependent probability models to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) data to obtain distributions of longitudinal antibody response and cytokine values. To assess differences between groups, an overlap metric is applied to the modeled response curves. Our antibody models suggest significant differences between male and female populations and demonstrate deficient antibody responses of less-healthy groups such as smokers. Our cytokine …

Decoding Early Covid-19 Responses Using Mathematical Modeling Of Social Distancing Strategies Across Multiple Countries, Sri Gunturu, Suki Lewis, Katelyn Nguyen, Asma Azizi

Spora: A Journal of Biomathematics

During the early phase of the COVID-19 pandemic, before vaccines were available, countries implemented diverse combinations of social-distancing (SD) measures shaped by cultural norms and public acceptance. These differences produced varied outcomes in controlling viral spread, offering lessons for future health-crisis preparedness. We performed a reverse-engineering analysis of early COVID-19 case data from five socioculturally distinct countries—India, Vietnam, Italy, Finland, and the United States—selected to capture a range of initial prevalence levels. Using mathematical modeling and data fitting, we inferred the relative contributions of three SD interventions: face masking, quarantine, and isolation of infected individuals. We then employed an efficiency …

Effects Of Desiccation On Invasive Faucet Snail (Bithynia Tentaculata) And Trematode Survival, Elise Marie Jordahl

Graduate Research Theses & Dissertations

Parasitism is one of the most common and diverse life history strategies, yet relatively little is known about the role of parasites as invasive species. Invasive species, which present one of the greatest threats to biodiversity, often need to overcome adverse environmental conditions as they establish and spread in new habitats. Invasive parasites are subject to these same conditions, though the effects may be mediated through their hosts. Here, I use an invasive snail and its trematode parasites to quantify the effects of desiccation on survival to better understand how processes of invasion play out in host-parasite systems. The faucet …

The Effect Of Sex On A-To-I Editing In Skeletal Muscle During Inflammation, Skyler Lee

Graduate Theses/Dissertations

Adenosine-to-inosine (A-to-I) RNA editing is a post-transcriptional mechanism mediated by ADAR enzymes that can alter RNA sequence, protein function, and gene regulation. Because ADAR1 is upregulated during inflammation and plays a critical role in innate immunity, previous studies investigated the effects of acute inflammation on RNA editing in male and female mice. Lipopolysaccharide (LPS) was used to induce inflammation, and RNA editing levels were examined in the heart, brain, and skeletal muscle. While editing levels in the heart and brain remained unchanged, skeletal muscle exhibited tissue- and sex-specific differences in editing. In this thesis, LPS treatment affected selective editing, increasing …

Surveillance Of A Novel Vesivirus Discovered In An Urban Mephitis Mephitis Population, Amanda E. Diggins

Honors Theses and Capstones

Caliciviridae is a family of non-enveloped, positive-sense, single stranded RNA viruses, including eleven defined genera that contain important pathogens of humans and animals. Within the Caliciviridae family, the genus Vesiviridae includes feline calicivirus, a leading cause of upper respiratory disease in cats, and vesicular exanthema of swine virus, a historical disease of domestic swine that has now been implicated in several marine mammal vesicular diseases, one of which has been confirmed zoonotic. Urban landscapes create a unique environment for rapid intra- and interspecies transmission of viruses. Clustered resources attract high-density populations of synanthropic wildlife species, increasing spatial overlap and heightening …

Tick Lipocalin Triggers Mammalian Igfbp-3-Mediated Apoptosis In Macrophages And Keratinocytes, Krittika Nandy, P. P. Mahesh, Lichao Liu, Daniel E. Sonenshine, Hameeda Sultana, Girish Neelakanta

Biological Sciences Faculty Publications

Ticks secrete several molecules, including lipocalins, in their saliva during blood feeding on a vertebrate host. In this study, we provide novel evidence on the role of Ornithodoros turicata americanus tick lipocalin (Otlip) in modulating cytokine expression and in triggering apoptosis in mammalian macrophages and keratinocytes. The cytokine array analysis revealed significantly increased secretion of insulin-like growth factor-binding protein 3 (IGFBP3) from murine macrophage cell line upon treatment with recombinant Otlip protein (rGST-Otlip) when compared to the secretion noted from cells treated with a control protein (rGST). Similar observation with cytokine protein array analysis was noted when murine macrophages were …

The Role Of Tumor Microenvironment In Glioblastoma Multiforme(Gbm) Therapeutic Resistance, Kwesi E. Taylor

Master's Theses or Doctor of Nursing Practice

Despite significant advances in cancer research and treatment, Glioblastoma multiforme (GBM) remains one of the most difficult cancers to treat effectively, with minimal improvement in long-term survival rates over the past few decades. This is largely attributed to tumor heterogeneity and the ability of tumor cells to develop adaptive resistance mechanisms supported by the tumor microenvironment (TME). Although the TME is recognized as a key contributor to tumor progression and therapeutic resistance, the underlying molecular pathways and regulatory genes remain incompletely understood. This study investigated the role of the tumor microenvironment in GBM therapeutic resistance using a bioinformatics approach. Single-cell …

Bayesian Multivariate Modelling Of Lone Star (Amblyomma Americanum) Tick Life Stage Abundance And Temporal Trends To Inform Public Health Risk In Virginia, Thabo Lephoto, Henry Mwambi, Oliver Bodhlyera, Holly Gaff

Biological Sciences Faculty Publications

The increasing abundance of ticks poses a growing public health concern due to heightened human exposure to tick bites. The lone star tick (Amblyomma americanum: Ixodida: Ixodidae), a common human-biting species in the United States, has expanded its range in recent years. However, how its different life stages vary across time, habitats, and locations remains insufficiently understood. We analyzed tick abundance data collected in southeastern Virginia between 2009 and 2018, focusing on larval, nymphal, and adult life stages. A Bayesian multivariate modelling framework was used to examine seasonal patterns, habitat effects, spatial variation, and biological links between life stages. Two …

The Rhesus Macaque Model Of Mycobacterium Avium Infection Reveals That Age-Related Disease Is Due In Part To Chronic Inflammation And Lung Microbial Dysbiosis, Ethan G. Napier

Theses and Dissertations--Microbiology, Immunology, and Molecular Genetics

Aging is associated with dysregulated immunity and increased susceptibility to infection, a phenomenon dubbed as immunosenescence and characterized by reduced naïve T and B cell pools, altered innate immune function, and chronic low-grade inflammation. Nontuberculous mycobacterial (NTM) pulmonary disease (NTMPD) is an increasingly relevant chronic lung infection that disproportionately affects older adults (65+ years) and immunocompromised individuals. However, the host factors underlying increased disease severity in aged patients remain poorly defined. Literature suggests that effective control of NTM relies on coordinated innate and adaptive immune responses, particularly macrophage activation and Th1 cytokine signaling. Using a rhesus macaque model that closely …