Immunology and Infectious Disease Commons^™

Advancements In Dendritic Cell Vaccination: Enhancing Efficacy And Optimizing Combinatorial Strategies For The Treatment Of Glioblastoma, Robert Subtirelu, Eric Teichner, Arjun Ashok, Chitra Parikh, Sahithi Talasila, Irina-Mihaela Matache, Ahab Alnemri, Victoria Anderson, Osmaan Shahid, Sricharvi Mannam, Andrew Lee, Thomas Werner, Mona-Elisabeth Revheim, Abass Alavi

Student Papers, Posters & Projects

Glioblastomas (GBM) are highly invasive, malignant primary brain tumors. The overall prognosis is poor, and management of GBMs remains a formidable challenge, necessitating novel therapeutic strategies such as dendritic cell vaccinations (DCVs). While many early clinical trials demonstrate an induction of an antitumoral immune response, outcomes are mixed and dependent on numerous factors that vary between trials. Optimization of DCVs is essential; the selection of GBM-specific antigens and the utilization of ¹⁸F-fludeoxyglucose Positron Emission Tomography (FDG-PET) may add significant value and ultimately improve outcomes for patients undergoing treatment for glioblastoma. This review provides an overview of the mechanism of …

Adaptive Design Of Mrna-Loaded Extracellular Vesicles For Targeted Immunotherapy Of Cancer, Shiyan Dong, Xuan Liu, Ye Bi, Yifan Wang, Abin Antony, Daeyong Lee, Kristin Huntoon, Seongdong Jeong, Yifan Ma, Xuefeng Li, Weiye Deng, Benjamin R Schrank, Adam J Grippin, Jonghoon Ha, Minjeong Kang, Mengyu Chang, Yarong Zhao, Rongze Sun, Xiangshi Sun, Jie Yang, Jiayi Chen, Sarah K Tang, L James Lee, Andrew S Lee, Lirong Teng, Shengnian Wang, Lesheng Teng, Betty Y S Kim, Zhaogang Yang, Wen Jiang

Faculty, Staff and Student Publications

The recent success of mRNA therapeutics against pathogenic infections has increased interest in their use for other human diseases including cancer. However, the precise delivery of the genetic cargo to cells and tissues of interest remains challenging. Here, we show an adaptive strategy that enables the docking of different targeting ligands onto the surface of mRNA-loaded small extracellular vesicles (sEVs). This is achieved by using a microfluidic electroporation approach in which a combination of nano- and milli-second pulses produces large amounts of IFN-γ mRNA-loaded sEVs with CD64 overexpressed on their surface. The CD64 molecule serves as an adaptor to dock …

Development Of Targeted Drug Delivery System To Improve Immunotherapy In Pancreatic Cancer, Poornima Devi Shaji, Ana Martinez Bulnes, Nirnoy Dan, Subhash C. Chauhan, Sheema Khan, Murali M. Yallapu

Research Colloquium

Introduction: About 95% of tumor arises from epithelial cell lining ducts known to be pancreatic ductal adenocarcinomas, with less than 5-7% survival rate. Unfortunately, little progress has been seen in the outcomes of patients with PDAC as tumor develops high desmoplasia and chemo-resistance to chemotherapeutic drugs, such as gemcitabine (Gem). Immunotherapy has shown promising results in other cancers but limited response in pancreatic cancer due to desmoplasia and fibrotic tumor microenvironment. A recently identified mucin, MUC13 is aberrantly expressed in pancreatic tumors but not in normal pancreas. Due to its high membrane expression, MUC13 may serve as an excellent target …

D-Shaped Nematode Eggs In The Feces Of Rangifer Tarandus: A Story In Pictures, Olga A. Loginova

MANTER: Journal of Parasite Biodiversity

D-shaped nematode eggs in the feces of Rangifer tarandus are expected to be oxyurid nematodes (Nemata: Oxyurida) of the genus Skrjabinema. The species S. tarandi is considered species-specific for this host. There is no consensus regarding the cross-infection of reindeer and sheep with S. ovis and S. tarandi. The drawings proposed by descriptors complicate differential diagnostics. Micrographs of S. tarandi eggs obtained via light microscopy and scanning electron microscopy as well as photographs of S. ovis eggs and drawings made on their basis are proposed to confidently distinguish between representatives of these two species, taking into account morphometric data. Thus, …

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 …

Setd2 Loss And Atr Inhibition Synergize To Promote Cgas Signaling And Immunotherapy Response In Renal Cell Carcinoma, Xian-De Liu, Yan-Ting Zhang, Daniel J Mcgrail, Xuesong Zhang, Truong Lam, Anh Hoang, Elshad Hasanov, Ganiraju Manyam, Christine B Peterson, Haifeng Zhu, Shwetha V Kumar, Rehan Akbani, Patrick G Pilie, Nizar M Tannir, Guang Peng, Eric Jonasch

Faculty, Staff and Student Publications

PURPOSE: Immune checkpoint blockade (ICB) demonstrates durable clinical benefits in a minority of patients with renal cell carcinoma (RCC). We aimed to identify the molecular features that determine the response and develop approaches to enhance it.

EXPERIMENTAL DESIGN: We investigated the effects of SET domain-containing protein 2 (SETD2) loss on the DNA damage response pathway, the cytosolic DNA-sensing pathway, the tumor immune microenvironment, and the response to ataxia telangiectasia and rad3-related (ATR) and checkpoint inhibition in RCC.

RESULTS: ATR inhibition activated the cyclic GMP-AMP synthase (cGAS)-interferon regulatory factor 3 (IRF3)-dependent cytosolic DNA-sensing pathway, resulting in the concurrent expression of inflammatory …

Modified Vaccine Vectors To Understand Adjuvant Functions Of Listeria During Chronic Schistosomiasis, Stephanie K. Norwood

Biological Sciences Theses & Dissertations

Vaccination is one of the most effective strategies employed to prevent infectious diseases. Successful vaccination is dependent upon the induction of a specific, robust, and prolonged immune response. One of the major challenges faced by vaccine development is vaccine failure due to host-related factors that can modulate the immune system, which leads to non-responsiveness to vaccinations. The generation of new vaccine strategies is imperative to combat these effects. Live bacterial vectors are one approach used as they can elicit humoral immunity, cellular immunity, or both. Listeria monocytogenes is a Gram positive, intracellular pathogen that is an effective bacterial vaccine vector …

Dense Granule Protein 3 Of Toxoplasma Gondii Plays A Crucial Role In The Capability Of The Tissue Cysts Of The Parasite To Persist In The Presence Of Anti-Cyst Cd8+ T Cells During The Chronic Stage Of Infection, Rajesh Mani, Mohamed H. Abdelaziz, Eri Ochiai, Qila Sa, Barbara A. Fox, David J. Bzik, Yasuhiro Suzuki

Markey Cancer Center Faculty Publications

Toxoplasma gondii establishes chronic infection by forming tissue cysts, and this chronic infection is one of the most common parasitic infections in humans. Our recent studies revealed that whereas CD8 + T cells of genetically resistant BALB/c mice have the capability to remove the tissue cysts of the parasite through their perforin-mediated activities, small portions of the cysts are capable of persisting in the presence of the anti-cyst CD8+ T cells. It is currently unknown how those small portions of the cysts resist or escape the T-cell immunity and persist in the hosts. In the present study, we discovered that …

Inhibition Of Mitochondrial Fission Activates Glycogen Synthesis To Support Cell Survival In Colon Cancer, Sumati Raj Hasani, Lyndsay E. A. Young, Warren Van Nort, Moumita Banerjee, Dylan R. Rivas, Jinhwan Kim, Xiaopeng Xiong, Ramon C. Sun, Matthew S. Gentry, Hiromi Sesaki, Tianyan Gao

Markey Cancer Center Faculty Publications

Metabolic reprogramming has been recognized as one of the major mechanisms that fuel tumor initiation and progression. Our previous studies demonstrate that activation of Drp1 promotes fatty acid oxidation and downstream Wnt signaling. Here we investigate the role of Drp1 in regulating glycogen metabolism in colon cancer. Knockdown of Drp1 decreases mitochondrial respiration without increasing glycolysis. Analysis of cellular metabolites reveals that the levels of glucose-6-phosphate, a precursor for glycogenesis, are significantly elevated whereas pyruvate and other TCA cycle metabolites remain unchanged in Drp1 knockdown cells. Additionally, silencing Drp1 activates AMPK to stimulate the expression glycogen synthase 1 (GYS1) mRNA …

Combination Therapy Of Triple-Negative Breast Cancer With Paclitaxel And Ambrisentan, A Selective Antagonist Of The Endothelin Type A Receptor, Inhibits Tumor Growth And Metastasis, Farah Nasser Almahrook

Theses

Cancer treatment is a big challenge especially when associated with metastasis. Moreover, the importance of using combination therapy is increasing, especially for highly invasive, drug-resistant cancers, such as triple-negative breast cancer (TNBC). Ambrisentan, a selective antagonist of the endothelin type A receptor (ETAR) was previously shown to reduce metastasis of TNBC in a preclinical tumor model when used prophylactically. In the current study, we investigated the therapeutic potential of Ambrisentan, given as monotherapy or in combination with Paclitaxel, on TNBC. The data show that oral dosing with Ambrisentan led to a significant retardation in tumor growth and metastasis. Moreover, combining …

Pd-1 Blockade In Combination With Dasatinib Potentiates Induction Of Anti-Acute Lymphocytic Leukemia Immunity, Paul Koller, Natalia Baran, Karine Harutyunyan, Antonio Cavazos, Saradhi Mallampati, Renee L Chin, Zhou Jiang, Xian Sun, Heng-Huan Lee, Jennifer L Hsu, Patrick Williams, Xuelin Huang, Michael A Curran, Mien-Chie Hung, Marina Konopleva

Faculty, Staff and Student Publications

Immunotherapy, in the form of hematopoietic stem cell transplantation (HSCT), has been part of the standard of care in the treatment of acute leukemia for over 40 years. Trials evaluating novel immunotherapeutic approaches, such as targeting the programmed death-1 (PD-1) pathway, have unfortunately not yielded comparable results to those seen in solid tumors. Major histocompatibility complex (MHC) proteins are cell surface proteins essential for the adaptive immune system to recognize self versus non-self. MHC typing is used to determine donor compatibility when evaluating patients for HSCT. Recently, loss of MHC class II (MHC II) was shown to be a mechanism …

Multiple Rsv Strains Infecting Hep-2 And A549 Cells Reveal Cell Line-Dependent Differences In Resistance To Rsv Infection, Anubama Rajan, Felipe-Andres Piedra, Letisha Aideyan, Trevor Mcbride, Matthew Robertson, Hannah L. Johnson, Gina Marie Aloisio, David Henke, Cristian Coarfa, Fabio Stossi, Vipin Kumar Menon, Harshavardhan Doddapaneni, Donna Marie Muzny, Sara Joan Javornik Cregeen, Kristi Louise Hoffman, Joseph Petrosino, Richard A. Gibbs, Vasanthi Avadhanula, Pedro A. Piedra

Research Symposium

Background: Respiratory syncytial virus (RSV) is the major viral driver of a global pediatric respiratory disease burden disproportionately borne by the poor¹. Thus, RSV, like SARS-CoV-2, combines with congenital and environmental and host-history-dependent factors to create a spectrum of disease with greatest severity most frequently occurring in those least able to procure treatment.

Methods: Here we apply whole genome sequencing and a suite of other molecular biological techniques to survey host-virus dynamics in infections of two distinct cell lines (HEp2 and A549) with four strains representative of known RSV genetic diversity.

Results: We observed non-gradient patterns of RSV …

Immunepotent Crp Enhances Cyclophosphamide-Induced Cytotoxicity Through A Caspase Independent But Ros Dependent Mechanism In Triple Negative-Breast Cancer Cells, Ana L. Rivera, A. C. Martínez-Torres, C. Rodríguez-Padilla

Research Symposium

Background: Breast cancer (BC) is one of the leading causes of cancer death worldwide. Cyclophosphamide (CYP) remains a mainstay in cancer therapy mainly in the triple negative breast cancer subtype (TNBC) in spite of harmful adverse effects and cell death-resistances. To face this, combination of chemotherapies and immunotherapies has been proposed. IMMUNEPOTENT CRP (ICRP) is an immunotherapy that has cytotoxic effects in several cancer cells without affecting peripheral blood mononuclear cells (PBMC) and CD3+ cells, beside improving clinical parameters of chemotherapy-treated patients. The aim of this study was to evaluate the mechanism of cytotoxicity induced by ICRP in combination with …

Antibody Mediated Targeted Drug Delivery System To Improve Immunotherapy In Pancreatic Cancer, Poornima Devi Shaji, Meena Jaggi, Murali M. Yallapu, Subhash C. Chauhan, Sheema Khan

Research Symposium

About 95% of tumor arises from epithelial cell lining ducts known to be pancreatic ductal adenocarcinomas, with less than 5-7% survival rate. Unfortunately, little progress has been seen in the outcomes of patients with PDAC as tumor develops high desmoplasia and chemo-resistance to chemotherapeutic drugs, such as gemcitabine (Gem). Immunotherapy has shown promising results in cancers, except pancreatic cancer due to their characteristic fibrotic tumor microenvironment. The therapies are unable to penetrate to the fibrotic tumors leading to insufficient availability of the therapeutic drugs at the tumor site. A recently identified mucin, MUC13 is aberrantly expressed in pancreatic tumors but …

Homoeopathic Medicines Modulate Inflammatory Functions And Adhesion Receptor Expression In Human Blood Cells: An In Vitro Study, Nibedita Dalpati, Shubham Kumar Rai, Divya Singh, Shiba Prasad Dash, Sukanti S. Sarangi, Mahabahu Nayak, Pranita P. Sarangi

Indian Journal of Research in Homoeopathy

Background: Homoeopathic medicines are used extensively for the treatment of many human diseases and are shown to affect immune cell functions. However, our understanding of the immunomodulatory effects of such medicines and associated mechanisms of action remains limited. Objectives: The present study aims to investigate the immunomodulatory effects of Arsenic album, Rhus toxicodendron, Hepar sulphuris and Bryonia alba on lipopolysaccharide (LPS) induced peripheral blood neutrophils and monocytes. Materials and Methods: In this work, neutrophils and monocytes were treated with different homoeopathic dilutions of 30C potency separately, followed by stimulation with the LPS, to examine the immunomodulatory effects of these …

Transgenic Mice Expressing Functional Tcrs Specific To Cardiac Myhc-Α 334–352 On Both Cd4 And Cd8 T Cells Are Resistant To The Development Of Myocarditis On C57bl/6 Genetic Background, Meghna Sur, Mahima T. Rasquinha, Rajkumar Arumugam, Chandirasegaran Massilamany, Arunkumar Gangaplara, Kiruthiga Mone, Ninaad Lasrado, Bharathi Yalaka, Aakash Doiphode, Channabasavaiah Gurumurthy, David J. Steffen, Jay Reddy

School of Veterinary and Biomedical Sciences: Faculty Publications

Myocarditis is a predominant cause of congestive heart failure and sudden death in children and young adolescents that can lead to dilated cardiomyopathy. Lymphocytic myocarditis mediated by T cells can result from the recognition of cardiac antigens that may involve CD4 or CD8 T cells or both. In this report, we describe the generation of T cell receptor (TCR) transgenic mice on a C57BL/6 genetic background specific to cardiac myosin heavy chain (Myhc)-α 334–352 and make the following observations: First, we verified that Myhc-α 334–352 was immunogenic in wild-type C57BL/6 mice and induced antigen-specific CD4 T cell responses despite being …

Methionine Biosynthesis Enzyme Momet2 Is Required For Rice Blast Fungus Pathogenicity By Promoting Virulence Gene Expression Via Reducing 5mc Modification, Huimin Li, Pengcheng Mo, Jun Zhang, Zhuoer Xie, Xinyu Liu, Han Chen, Leiyun Yang, Muxing Liu, Haifeng Zhang, Ping Wang, Zhengguang Zhang

School of Medicine Faculty Publications

The emergence of fungicide resistance severely threatens crop production by limiting the availability and application of established fungicides. Therefore, it is urgent to identify new fungicidal targets for controlling plant diseases. Here, we characterized the function of a conserved homoserine O-acetyltransferase (HOA) from the rice blast fungus Magnaporthe oryzae that could serve as the candidate antifungal target. Deletion of the MoMET2 and MoCYS2 genes encoding HOAs perturbed the biosynthesis of methionine and S-adenyl methionine, a methyl group donor for epigenetic modifications, and severely attenuated the development and virulence of M. oryzae. The ΔMomet2 mutant is significantly increased in 5-methylcytosine (5mC) …

A Naturally Derived Watercress Flower-Based Phenethyl Isothiocyanate-Enriched Extract Induces The Activation Of Intrinsic Apoptosis Via Subcellular Ultrastructural And Ca2+ Efflux Alterations In An In Vitro Model Of Human Malignant Melanoma, Sotiris Kyriakou, Louiza Potamiti, Nikoletta Demosthenous, Tom Amery, Kyle Stewart, Paul G. Winyard, Rodrigo Franco, Aglaia Pappa, Mihalis I. Panayiotidis

School of Veterinary and Biomedical Sciences: Faculty Publications

The aim of the current study was to (i) extract isolated fractions of watercress flowers enriched in polyphenols, phenethyl isothiocyanate and glucosinolates and (ii) characterize the anticancer mode of action of non-lethal, sub-lethal and lethal concentrations of the most potent extract fraction in primary (A375) and metastatic (COLO-679) melanoma cells as well as non-tumorigenic immortalized keratinocyte (HaCaT) cells. Cytotoxicity was assessed via the Alamar Blue assay, whereas ultrastructural alterations in mitochondria and the endoplasmic reticulum were determined via transmission electron microscopy. Mitochondrial membrane depolarization was determined using Mito-MP dye, whereas apoptosis was evaluated through the activation of caspases-3, -8 and …

Biosafety And Biohazard Considerations Of Hsv-1-Based Oncolytic Viral Immunotherapy., Elizabeth Robilotti, Nathalie C Zeitouni, Marlana Orloff

Department of Medical Oncology Faculty Papers

Oncolytic viral immunotherapies are agents which can directly kill tumor cells and activate an immune response. Oncolytic viruses (OVs) range from native/unmodified viruses to genetically modified, attenuated viruses with the capacity to preferentially replicate in and kill tumors, leaving normal tissue unharmed. Talimogene laherparepvec (T-VEC) is the only OV approved for patient use in the United States; however, during the last 20 years, there have been a substantial number of clinical trials using OV immunotherapies across a broad range of cancers. Like T-VEC, many OV immunotherapies in clinical development are based on the herpes simplex virus type 1 (HSV-1), with …

Stereotactic Ablative Radiotherapy With Or Without Immunotherapy For Early-Stage Or Isolated Lung Parenchymal Recurrent Node-Negative Non-Small-Cell Lung Cancer: An Open-Label, Randomised, Phase 2 Trial, Joe Y Chang, Steven H Lin, Wenli Dong, Zhongxing Liao, Saumil J Gandhi, Carl M Gay, Jianjun Zhang, Stephen G Chun, Yasir Y Elamin, Frank V Fossella, George Blumenschein, Tina Cascone, Xiuning Le, Jenny V Pozadzides, Anne Tsao, Vivek Verma, James W Welsh, Aileen B Chen, Mehmet Altan, Reza J Mehran, Ara A Vaporciyan, Stephen G Swisher, Peter A Balter, Junya Fujimoto, Ignacio I Wistuba, Lei Feng, J Jack Lee, John V Heymach

Faculty, Staff and Student Publications

BACKGROUND: Stereotactic ablative radiotherapy (SABR) is the standard treatment for medically inoperable early-stage non-small-cell lung cancer (NSCLC), but regional or distant relapses, or both, are common. Immunotherapy reduces recurrence and improves survival in people with stage III NSCLC after chemoradiotherapy, but its utility in stage I and II cases is unclear. We therefore conducted a randomised phase 2 trial of SABR alone compared with SABR with immunotherapy (I-SABR) for people with early-stage NSCLC.

METHODS: We did an open-label, randomised, phase 2 trial comparing SABR to I-SABR, conducted at three different hospitals in TX, USA. People aged 18 years or older …

Color Stability, Physical Properties And Antifungal Effects Of Zro2 Additions To Experimental Maxillofacial Silicones: Comparisons With Tio2, Mazen Alkahtany, Mark W. Beatty, Fahd Alsalleeh, Thomas M. Petro, Bobby Simetich, You Zhou, Dennis Feely, Grigoris Polyzois

School of Veterinary and Biomedical Sciences: Faculty Publications

(1) Background: Color changes, physical degradation, and fungal infections are challenges to the longevity of maxillofacial polydimethylsiloxane (PDMS) elastomers. This study aimed to evaluate color changes, physical properties, and antifungal properties of PDMS loaded with ZrO₂ and TiO₂ submicron- and nano-sized particles. (2) Methods: A 1% weight of 40 nm or 200 nm diameter ZrO₂ or TiO₂ nanoparticles was mixed into PDMS with 2% functional intrinsic yellow pigment and polymerized. Control materials contained 13% weight 200 nm silica. Samples were exposed to 3000 h of UVB radiation (200 μW/cm²) or darkness. Color parameters L*a*b* …

An Evolutionary Pathway For Coping With Emerging Infectious Disease, Scott Lyell Gardner, Daniel R. Brooks, Walter A. Boeger, Eric P. Hoberg

Zea E-Books Collection

Emerging infectious disease (EID) represents an existential threat to humanity. EIDs are increasing in frequency and impact because of climate change and other human activities. We are losing the battle against EIDs because of improper assessment of the risk of EID. This stems from adherence to a failed paradigm of pathogen-host associations that suggests EIDs ought to be both unpredictable and rare. That, in turn, leads to policies suggesting that crisis response is the best we can do. Real-time and phylogenetic assessments show EIDs to be neither rare nor unpredictable—this is the parasite paradox that shows the failures of the …

Gregarine Parasites In Zygoptera Of Keith County, Ne, Anisha Kadubandi, B. Gage Kircher Ii, Scott L. Gardner

UCARE: Research Products

Prevalence of Gregarine Protozoa Infection in Zygoptera Sourced from Varying Collection Sites in Keith County, Nebraska

B.G Kircher II, A. Kadubandi, and S.L. Gardner S. H.W. Manter Laboratory of Parasitology, University of Nebraska-Lincoln and Cedar Point Biological Station, University of Nebraska-Lincoln

Damselflies are ubiquitous flying insects of the order Odonata with thousands of species found around the world. The parasites associated with damselfly species are equally as ubiquitous, with the most common being gregarine protozoa and water mites, though other parasitic organisms such as trematodes are also found in these animals. Gaining an understanding of the relationships among hosts and …

Protocol For Optimizing Production And Quality Control Of Infective Ecohiv Virions, Hammodah Rawhi Hammodah Alfar, Daphne N. Pariser, Harry Chanzu, Smita Joshi, Daniёlle M. Coenen, Joshua Lykins, Kanakanagavalli Shravani Prakhya, Mary Jane Potash, Wei Chao, Jennifer Kelschenbach, David J. Volsky, Kelly Metcalf-Pate

Saha Cardiovascular Research Center Faculty Publications

EcoHIV is a model of HIV infection that recapitulates aspects of HIV-1 pathology in mice. However, there are limited published protocols to guide EcoHIV virion production. Here, we present a protocol for producing infective EcoHIV virions and essential quality controls. We describe steps for viral purification, titering, and multiple techniques to analyze infection efficacy. This protocol produces high infectivity in C57BL/6 mice which will aid investigators in generating preclinical data.

Hla-Ii-Dependent Neuroimmune Changes In Group A Streptococcal Necrotizing Fasciitis, Ganesh Ambigapathy, Santhosh Mukundan, Kumi Nagamoto-Combs, Colin Combs, Suba Nookala

Biomedical Sciences Faculty Publications

Streptococcus pyogenes (Group A Streptococcus, GAS) bacteria cause a spectrum of human diseases ranging from self-limiting pharyngitis and mild, uncomplicated skin infections (impetigo, erysipelas, and cellulitis) to highly morbid and rapidly invasive, life-threatening infections such as streptococcal toxic shock syndrome and necrotizing fasciitis (NF). HLA class II allelic polymorphisms are linked with differential outcomes and severity of GAS infections. The dysregulated immune response and peripheral cytokine storm elicited due to invasive GAS infections increase the risk for toxic shock and multiple organ failure in genetically susceptible individuals. We hypothesized that, while the host immune mediators regulate the immune responses against …

Antimicrobial Mitochondrial Reactive Oxygen Species Induction By Lung Epithelial Immunometabolic Modulation, Yongxing Wang, Vikram V Kulkarni, Jezreel Pantaleón García, Miguel M Leiva-Juárez, David L Goldblatt, Fahad Gulraiz, Lisandra Vila Ellis, Jichao Chen, Michael K Longmire, Sri Ramya Donepudi, Philip L Lorenzi, Hao Wang, Lee-Jun Wong, Michael J Tuvim, Scott E Evans

Faculty, Staff and Student Publications

Pneumonia is a worldwide threat, making discovery of novel means to combat lower respiratory tract infection an urgent need. Manipulating the lungs' intrinsic host defenses by therapeutic delivery of certain pathogen-associated molecular patterns protects mice against pneumonia in a reactive oxygen species (ROS)-dependent manner. Here we show that antimicrobial ROS are induced from lung epithelial cells by interactions of CpG oligodeoxynucleotides (ODN) with mitochondrial voltage-dependent anion channel 1 (VDAC1). The ODN-VDAC1 interaction alters cellular ATP/ADP/AMP localization, increases delivery of electrons to the electron transport chain (ETC), increases mitochondrial membrane potential (ΔΨm), differentially modulates ETC complex activities and consequently results in …

Autotaxin Suppresses Cytotoxic T Cells Via Lpar5 To Promote Anti-Pd-1 Resistance In Non-Small Cell Lung Cancer, Jessica M Konen, B Leticia Rodriguez, Haoyi Wu, Jared J Fradette, Laura Gibson, Lixia Diao, Jing Wang, Stephanie Schmidt, Ignacio I Wistuba, Jianjun Zhang, Don L Gibbons

Faculty, Staff and Student Publications

Non-small cell lung cancers that harbor concurrent KRAS and TP53 (KP) mutations are immunologically warm tumors with partial responsiveness to anti-PD-(L)1 blockade; however, most patients observe little or no durable clinical benefit. To identify novel tumor-driven resistance mechanisms, we developed a panel of KP murine lung cancer models with intrinsic resistance to anti-PD-1 and queried differential gene expression between these tumors and anti-PD-1-sensitive tumors. We found that the enzyme autotaxin (ATX), and the metabolite it produces, lysophosphatidic acid (LPA), were significantly upregulated in resistant tumors and that ATX directly modulated antitumor immunity, with its expression negatively correlating with total and …

Evaluation Of Clostridium Septicum Hemolytic Activity, Administration Route, And Dosage Volume Of A Clostridial Dermatitis (Cellulitis) Bacterin-Toxoid On Humoral Immune Response In Commercial Turkeys, Aaron Forga, Kabel Robbins, Andrew Smith, Makenly Coles, Guillermo Tellez-Isaias, Christine N. Vuong, Billy Hargis, Danielle Graham

Poultry Science Faculty Publications and Presentations

Clostridial cellulitis or dermatitis affects commercial turkey flocks, primarily as they approach market age. In the field, this disease has been effectively controlled with antibiotics, but alternatives to antibiotics are needed. Bacterin-toxoid vaccination programs have been shown to prevent clostridial diseases in other species, including humans. Results from previous field studies indicate that vaccination with an experimental whole-cell Clostridium septicum (CS) bacterin-toxoid oil emulsion vaccine reduced clostridial dermatitis-associated mortality and antibiotic usage for some commercial turkey flocks, but vaccination was not always efficacious. To improve vaccine efficacy, studies were conducted to optimize the antigenic component of the experimental …

Cytokine Data For Cytokine Profile Assessment From Peruvian Pinniped (Arctocephalus Australis And Otaria Byronia) Plasma, Mykenzee Munaco, Milton Levin, Michael Adkesson, Susana Cárdenas-Alayzad, Dimitrios G. Giarikos, Amy C. Hirons

SECLER Data

Large colonies of two vulnerable, sympatric pinniped species, Peruvian fur seals (Arctocephalus australis Peruvian subpopulation; PFS) and South American sea lions (Otaria byronia; SASL), reside and reproduce in Punta San Juan, Peru (PSJ) where they are exposed to stressors such as contaminants and El Niño Southern Oscillation (ENSO) events. The use of cytokines as immune biomarkers can be indicative of an animal’s health and function by allowing for the assessment of an individual's cytokine balance as type I helper T cells (Th1) or type II helper T cells (Th2) dominant. Utilizing archived pinniped plasma samples from 2009-2019 …

Leucocytozoon Cariamae N. Sp. And Haemoproteus Pulcher Coinfection In Cariama Cristata (Aves: Cariamiformes): First Mitochondrial Genome Analysis And Morphological Description Of A Leucocytozoid In Brazil, Lis Marques De C. Vieira, Pedro Henrique O. Pereira, Daniel Ambrózio Da Rocha Vilela, Irène Landau, M. Andreína Pacheco, Ananias A. Escalante, Francisco C. Ferreira, Érika Martins Braga

Harold W. Manter Laboratory of Parasitology: Library Materials

The distribution of avian haemosporidians of the genus Leucocytozoon in the Neotropics remains poorly understood. Recent studies confirmed their presence in the region using molecular techniques alone, but evidence for gametocytes and data on putative competent hosts for Leucocytozoon are still lacking outside highland areas. We combined morphological and molecular data to characterize a new Leucocytozoon species infecting a non-migratory red-legged seriema (Cariama cristata), the first report of a competent host for Leucocytozoon in Brazil. Leucocytozoon cariamae n. sp. is distinguished from the Leucocytozoon fringillinarum group by its microgametocytes that are not strongly appressed to the host cell …