Immunology and Infectious Disease Commons^™

High Fat, High Sucrose Diet Promotes Increased Expression Of Ace2 Receptor In The Siv-Infected Host: Implications For Sars-Cov-2 Infection, Elizabeth C. Delery, Danielle E. Levitt, Angela M. Amedee, Patricia E. Molina, Liz Simon

School of Graduate Studies Faculty Publications

Introduction: People with pre-existing conditions, including metabolic comorbidities, are at greater risk for complications of SARS-CoV-2 infection and expression of machinery required for viral entry into host cells may be a contributing factor. This study tested the hypothesis that high fat, high sucrose diet (HFSD) and alcohol use increase expression of angiotensin converting enzyme 2 (ACE2) receptor and transmembrane serine protease 2 (TMPRSS2) in tissues isolated from simian immunodeficiency virus (SIV) infected macaques, the most clinically relevant model for the study of HIV. Methods: Biospecimens obtained from a longitudinal study of SIV-infected, antiretroviral therapy (ART)-treated female rhesus macaques (Macaca mulatta) …

Broad Applicability Of The Goldspire™ Platform For The Treatment Of Solid Tumors, Jenny Zilberberg, Christopher Uhl, Charles B Scott, David W. Andrews, Mark A Exley

Department of Neurosurgery Faculty Papers

Goldspire™ is a personalized immunotherapy platform that combines whole tumor-derived cells with antisense oligonucleotide (IMV-001) against Insulin-Like Growth Factor-1 Receptor (IGF-1R) in biodiffusion chambers (BDCs; 0.1 μm pore). BDCs are exposed to 5-6 Gy and implanted at abdominal sites for ∼48 h to deliver an antigenic payload and immunostimulatory factors to train the immune system. Lead product IGV-001 was evaluated in newly diagnosed glioblastoma (ndGBM) patients in Phase 1a and 1b trials (NCT02507583). A Phase 2b study (NCT04485949) recently completed enrollment. Preventative treatment with tumor-specific products manufactured with Goldspire limited tumor progression and extended overall survival in mice challenged with …

Mta-Cooperative Prmt5 Inhibitors Enhance T Cell-Mediated Antitumor Activity In Mtap-Loss Tumors, Si Chen, Jiakai Hou, Roshni Jaffery, Ashley Guerrero, Rongjie Fu, Leilei Shi, Ningbo Zheng, Ritu Bohat, Nicholas A Egan, Chengtai Yu, Sana Sharif, Yue Lu, Wei He, Shuyue Wang, Donjeta Gjuka, Everett M Stone, Pooja Anil Shah, Jordi Rodon Ahnert, Taiping Chen, Xinli Liu, Mark T Bedford, Han Xu, Weiyi Peng

Faculty, Staff and Student Publications

BACKGROUND: Hyperactivated protein arginine methyltransferases (PRMTs) are implicated in human cancers. Inhibiting tumor intrinsic PRMT5 was reported to potentiate antitumor immune responses, highlighting the possibility of combining PRMT5 inhibitors (PRMT5i) with cancer immunotherapy. However, global suppression of PRMT5 activity impairs the effector functions of immune cells. Here, we sought to identify strategies to specifically inhibit PRMT5 activity in tumor tissues and develop effective PRMT5i-based immuno-oncology (IO) combinations for cancer treatment, particularly for methylthioadenosine phosphorylase (MTAP)-loss cancer.

METHODS: Isogeneic tumor lines with and without MTAP loss were generated by CRISPR/Cas9 knockout. The effects of two PRMT5 inhibitors (GSK3326595 and MRTX1719) were …

Fatal Disseminated Toxoplasmosis In Captive Red Kangaroo (Macropus Rufus) And Parma Wallaby (Macropus Parma): Pathological And Immunohistochemical Investigations, Sawang Kesdangsakonwut

The Thai Journal of Veterinary Medicine

Abstract

Toxoplasmosis is a protozoan zoonosis caused by Toxoplasma gondii. Marsupials are considered a susceptible intermediate host. T. gondii is mainly transmitted to intermediate hosts via the fecal-oral route. A captive red kangaroo was diagnosed with disseminated toxoplasmosis based on clinicopathological and immunohistochemical (IHC) investigations. Two years later, a five-year-old Parma wallaby was kept in the same area as the red kangaroo and showed clinical signs of depression, withdrawal from the troop, and weakness. The wallaby died within two days after showing the clinical signs. Pathological findings in this wallaby were compatible with disseminated toxoplasmosis. Tachyzoites and tissue cysts …

Novel Hamster Models Of Chikungunya Viral Arthritis, Tian Wang, Zhongde Wang

Funded Research Records

No abstract provided.

Molecular Detection Of Mycoplasma Spp. And Its Associated Risk Factors In Domestic Cats In The City Of Ibagué, Tolima, Karen D. Osorio Muñoz Dr., Iang S. Rondon Barragan Prof.

The Thai Journal of Veterinary Medicine

Feline hemoplasmosis is a disease with worldwide distribution, mainly in tropical countries, where its transmission is favored by the presence of vectors such as fleas and ticks. In Colombia, the diagnosis of the disease in small animals has been limited to the identification of the pathogen in blood smears, which have low sensitivity and specificity, demanding methods of higher diagnostic value, such as those based on molecular techniques. The objective of the present study was to investigate the prevalence of Mycoplasma spp. in felines from the city of Ibagué using the PCR and the associated risk factors. Briefly, blood samples …

The Roles Of Cd4+ T Cell Help, Sex, And Dose In The Induction Of Protective Cd8+ T Cells Against A Lethal Poxvirus By Mrna-Lnp Vaccines, Samita Kafle, Brian Montoya, Lingjuan Tang, Ying Tam, Hiromi Muramatsu, Norbert Pardi, Luis Sigal

Department of Microbiology and Immunology Faculty Papers

The role of CD4⁺ T cells in the induction of protective CD8⁺ T cells by mRNA lipid nanoparticle (LNP) vaccines is unknown. We used B6 or Tlr9^−/− mice depleted or not of CD4⁺ T cells and LNP vaccines loaded with mRNAs encoding the ectromelia virus (ECTV) MHC class I H-2 K^b-restricted immunodominant CD8⁺ T cell epitope TSYKFESV (TSYKFESV mRNA-LNPs) or the ECTV EVM158 protein, which contains TSYKFESV (EVM-158 mRNA-LNPs). Following prime and boost with 10 μg of either vaccine, K^b-TSYKFESV-specific CD8⁺ T cells fully protected male and female mice from …

Cognition And Inflammation In Youth With Perinatal Hiv, Megan Niehaus, Julie Mannarino, Jacob Bolzenius, Tori Frerichs, Robert Paul

Undergraduate Research Symposium

Background: Perinatally acquired HIV (PHIV) remains a major global health challenge. Approximately 90% of the global population of PHIV reside in low- or middle-income countries (LMICs) where access to antiretroviral therapy (ART) remains incomplete, particularly for PHIV. With PHIV, the brain is exposed to the virus during critical periods of brain development without the immunological benefits from ART. Unlike adults with horizontally acquired HIV whose nadir CD4+ Tcell count is a strong correlate of cognitive difficulties that persist after sustained use of ART, cognitive symptoms among PHIV youth are independent of traditional HIV disease metrics. Prior studies indicate that PHIV …

Root Lesion And Burrowing Nematodes And Their Management, Department Of Primary Industries And Regional Development, Western Australia

Grains and other field crops factsheets

Nematodes are common soil pests that feed on the roots of a wide range of crops in all agricultural areas of Western Australia, resulting in significant crop yield loss. Root lesion nematode can be managed but not eradicated.

This factsheet summarises the biology of the root lesion nematode (RLN, Pratylenchus spp.) and burrowing nematode (Radopholus spp.) species that damage Western Australian (WA) crops, and their diagnosis and management.

Armyworms And Their Management In Cereal Crops, Department Of Primary Industries And Regional Development, Western Australia

Grains and other field crops factsheets

Armyworms are pests of cereals crops. They are frequently found along the south coast of Western Australia and occasionally in other grainbelt locations.

When barley crops are maturing in spring, large armyworm caterpillars climb plants and can chew through the stems, causing the heads to fall to the ground. Damage to wheat and oat crops occurs less frequently and is usually minor compared to damage in barley. Armyworms are seldom a serious problem in pastures.

Aphid Feeding Damage And Its Management In Cereal Crops, Department Of Primary Industries And Regional Development, Western Australia

Grains and other field crops factsheets

Adult and nymph aphids suck sap from cereal crops, with large populations, especially in winter and spring, limiting grain yield and size. This page relates to feeding damage from oat aphid (Rhopalosiphon padi) and corn aphid (Rhopalosiphon maidis) in the absence of virus, and Russian wheat aphid (Diuraphis noxia).

Characterization Of High-Risk-Other Human Papillomavirus Genotypes In Papanicolaou Tests, High-Grade Squamous Intraepithelial Lesions, And Cervical Cancer, Caitlin E. Witt, Elizabeth F. Sutton, Ashley M. Stansbury, Ashley N. Winters, Luke C. Konur, Meng Luo, Jennifer E. Cameron, Beverly Ogden

School of Medicine Faculty Publications

Background: The objective of this study was to determine the human papillomavirus (HPV) genotypes of high-risk-other HPV Papanicolaou (Pap) tests and of biopsy tissues from patients with high-grade squamous intraepithelial lesion (HGSIL) or cervical cancer. High-risk-other HPV status was determined with the cobas HPV Test (Roche Diagnostics, North America) that identifies 12 high-risk, non-16/18 HPV genotypes. We hypothesized that we would find genotypes of HPV in our population that are not covered by the 9-valent HPV vaccine. Methods: For this retrospective cohort study, we randomly selected 50 high-risk-other HPV Pap test samples from 2018 from our pathology department registries for …

Understanding Primate Immunity To African Trypanosomes Through The Characterization Of Trypanosome Lytic Factor Formation And Function, Sara Fresard

Dissertations, Theses, and Capstone Projects

African trypanosomes cause an annual loss of over 1 billion USD due to their economic and agricultural burden in Sub-Saharan Africa. These parasites are unicellular, extracellular parasites, that infect humans, cattle, and other livestock. Humans and some non-human primates are protected against most species of trypanosomes due to an innate immunity factor, Trypanosome Lytic Factor (TLF). This modified High Density Lipoprotein (HDL) contains two unique proteins, Haptoglobin Related Protein (HPR), a ligand to a trypanosome surface receptor, and Apolipoprotein-L1 (APOL1), the lytic component. Our overall goal is to use our understanding of primate immunity to create genetically modified cattle that …

Exploring Berberine As A Novel Therapeutic Agent Against Staphylococcus Aureus Infections: Targeting Inflammation And Antibiotic Resistance, Daniel Kopulos

NYMC Student Theses and Dissertations

Staphylococcus aureus is a versatile Gram-positive bacterium commonly found on human skin. While often harmless, it can cause various infections when the skin is compromised, ranging from minor issues to life-threatening conditions in immunocompromised individuals.

The bacterium’s ability to resist antibiotics, particularly methicillin, underscores its clinical challenge. Staphylococcus aureus can also acquire vancomycin resistance. It evades immune responses through multiple mechanisms, including capsule formation, interference with immune proteins like staphylococcal protein A, and secretion of toxins such as Panton-Valentine Leukocidin. Understanding these mechanisms is crucial for developing effective strategies against Staphylococcus aureus infections.

The immune response to Staphylococcus aureus infections …

Combination Therapy Of Ido1 Inhibition And Anti-Pd1 Mediates Anti-Tumor Immunity By Promoting Memory Immunity Development And Cytotoxicity Of Γδ T And Nk Cells Via Il-2 Signaling And By Overcoming Pro-Tumor Effects Of Tgf-Β Signaling, Hyuk Jee

Dartmouth College Master’s Theses

Cutaneous melanoma is the most aggressive form of skin cancer even though it takes only about 1% of all skin cancers. Even among all cutaneous melanomas, NRAS-mutant melanoma is more aggressive than any other, and about 10-25% of all cutaneous melanoma cases have mutations in NRAS. NRAS is a member of the RAS family of proto-oncogenic GTPase proteins, and it plays a key role in signal transduction pathways responsible for cellular survival, proliferation, and metabolism. Immunotherapy is the first line of defense against NRAS-mutant melanoma because, despite tremendous efforts made for decades, it has not been successful to develop small …

Testing Strategies To Develop A Mucosal T Cell Inducing Vaccine For Hiv-1, Reynolds Boone

Master's Theses

Despite numerous efforts, HIV vaccine is still not available. Because HIV Envelop protein varies among subtypes and isolates, it is impossible for one vaccine against HIV Env to induce neutralizing antibodies against all subtypes and isolates. Previous vaccine attempts inducing HIV-specific CD4+ T cells have even been shown to enhance the HIV infection because HIV preferentially infects activated CD4+ T cells. It is known that CD8+ cytotoxic T cells (CTLs) play an important role in controlling HIV infections. We hypothesize that a vaccine inducing only CD8+ CTLs but not CD4+ T cells will be effective in preventing HIV infections. Thus, …

The Anti-Inflammatory Properties Of Exopolysaccharide From Bacillus Subtilis, Nikolay Todorov

Master's Theses

Commensal microorganisms can be used therapeutically to ameliorate a variety of diseases. The laboratory of Dr. Katherine L. Knight studies these therapeutic properties in the commensal microorganism known as Bacillus subtilis. Previously, the Knight lab has demonstrated that B. subtilis can protect against colitis caused by Citrobacter rodentium suggesting that B. subtilis possesses anti-inflammatory properties. These properties are specific to the polysaccharide capsule of the microorganism known as exopolysaccharide or EPS. EPS can be produced and purified for study. EPS has been demonstrated to be protective in a variety of diseases such as allergic eosinophilia, sepsis, Graft versus Host disease, …

Characterization Of Cd11c-Expressing Gut-Associated T Cells, Ana Cvetkovic

Master's Theses

Our immune system is a remarkable defense network that protects our bodies from a range of threats. Its’ intricate machinery comprises of messenger and effector cells that work together to coordinate an effective immune response. Traditionally, T lymphocytes have been considered effectors: they receive instructions from messengers, known as Antigen Presenting Cells (APCs), that alter T-cell activation state and behavior. In the gut, Dendritic Cells (DCs) are the APCs that most often instruct T cells. To accomplish their messenger role, DCs express CD11c at high levels, a surface marker involved in cell-to-cell signaling and phagocytosis. As such, CD11c expression has …

Alternative Approaches To Live Attenuated Oral Rotavirus Vaccines, Makoye Mhozya Kanyema, Junhong Wang, Gui-Lian Yang, Xin Cao, Chunfeng Wang

The Thai Journal of Veterinary Medicine

Oral attenuated rotavirus vaccine is safe and effective in developed countries but, however, it is less effective in low income countries such as African and Asian countries. Low vaccine effectiveness in low-income countries is arising from a variety of sources such as maternal antibodies, chronic enteropathy and other enteric diseases such as cholera, typhoid, and parasitic diseases, as well as the microbiota. There is increasingly evidence related to the risk of intussusception for the oral vaccine. The development of effective and safer rotavirus vaccines, particularly, non-living candidates, is critical. The aim of this review therefore is to explore some of …

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 …