Immunology and Infectious Disease Commons^™

Concepts In Animal Parasitology: Master Bibliography, Sue Ann Gardner

Concepts in Animal Parasitology Textbook

Master bibliography for the open educational resource/open access textbook Concepts in Animal Parasitology, Scott L. Gardner and Sue Ann Gardner, editors, published by Zea Books, Lincoln, Nebraska, United States, 2024. This includes the references from literature cited and suggested supplemental reading.

Biological Insights From Plasma Proteomics Of Non-Small Cell Lung Cancer Patients Treated With Immunotherapy, Jair Bar, Raya Leibowitz, Niels Reinmuth, Astrid Ammendola, Eyal Jacob, Mor Moskovitz, Adva Levy-Barda, Michal Lotem, Rivka Katsenelson, Abed Agbarya, Mahmoud Abu-Amna, Maya Gottfried, Tatiana Harkovsky, Ido Wolf, Ella Tepper, Gil Loewenthal, Ben Yellin, Yehuda Brody, Nili Dahan, Maya Yanko, Coren Lahav, Michal Harel, Shani Raveh Shoval, Yehonatan Elon, Itamar Sela, Adam Dicker, Yuval Shaked

Department of Radiation Oncology Faculty Papers

INTRODUCTION: Immune checkpoint inhibitors have made a paradigm shift in the treatment of non-small cell lung cancer (NSCLC). However, clinical response varies widely and robust predictive biomarkers for patient stratification are lacking. Here, we characterize early on-treatment proteomic changes in blood plasma to gain a better understanding of treatment response and resistance.

METHODS: Pre-treatment (T0) and on-treatment (T1) plasma samples were collected from 225 NSCLC patients receiving PD-1/PD-L1 inhibitor-based regimens. Plasma was profiled using aptamer-based technology to quantify approximately 7000 plasma proteins per sample. Proteins displaying significant fold changes (T1:T0) were analyzed further to identify associations with clinical outcomes using …

Immunotherapy Resistance In Solid Tumors: Mechanisms And Potential Solutions, Daniel Lefler, Steven Manobianco, Babar Bashir

Kimmel Cancer Center Faculty Papers

While the emergence of immunotherapies has fundamentally altered the management of solid tumors, cancers exploit many complex biological mechanisms that result in resistance to these agents. These encompass a broad range of cellular activities - from modification of traditional paradigms of immunity via antigen presentation and immunoregulation to metabolic modifications and manipulation of the tumor microenvironment. Intervening on these intricate processes may provide clinical benefit in patients with solid tumors by overcoming resistance to immunotherapies, which is why it has become an area of tremendous research interest with practice-changing implications. This review details the major ways cancers avoid both natural …

The Mrna-Lnp Vaccines - The Good, The Bad And The Ugly?, Botond Z. Igyártó, Zhen Qin

Department of Microbiology and Immunology Faculty Papers

The mRNA-LNP vaccine has received much attention during the COVID-19 pandemic since it served as the basis of the most widely used SARS-CoV-2 vaccines in Western countries. Based on early clinical trial data, these vaccines were deemed safe and effective for all demographics. However, the latest data raise serious concerns about the safety and effectiveness of these vaccines. Here, we review some of the safety and efficacy concerns identified to date. We also discuss the potential mechanism of observed adverse events related to the use of these vaccines and whether they can be mitigated by alterations of this vaccine mechanism …

Tumor-Associated Antigen Targets For Novel Immune-Based Strategies In Prostate Cancer, Amman Bhasin, Patrick Mille, Aditya Eturi, Andrew Iskander, William Tester, Kevin Zarrabi

Kimmel Cancer Center Faculty Papers

Prostate cancer remains the most common malignancy among men in the United States. Advancements in androgen receptor signaling blockade have led to landmark approvals for its use in patients with locally advanced and metastatic disease. However, additional novel therapeutic strategies for both hormone-sensitive and castration-resistant diseases remain ongoing areas of study. Thus, we turn to the growth of immuno-oncology, which has led to improved treatment outcomes for a variety of hematologic and solid tumor malignancies. Prostate cancers have shown only modest results with immune checkpoint inhibition in published trials, and innovative strategies are now looking into enhancing cytotoxic T-cell activity …

Microbial Interactions Among Gardnerella, Prevotella And Fannyhessea Prior To Incident Bacterial Vaginosis: Protocol For A Prospective, Observational Study, Christina A. Muzny, Jacob H. Elnaggar, Lúcia G.V. Sousa, Ângela Lima, Kristal J. Aaron, Isaac C. Eastlund, Keonte J. Graves, Chaoling Dong, Olivia T. Van Gerwen, Meng Luo, Ashutosh Tamhane, Dustin Long, Nuno Cerca, Christopher M. Taylor

School of Graduate Studies Faculty Publications

Introduction The aetiology of bacterial vaginosis (BV), a biofilm-associated vaginal infection, remains unknown. Epidemiologic data suggest that it is sexually transmitted. BV is characterised by loss of lactic acid-producing lactobacilli and an increase in facultative and strict anaerobic bacteria. Gardnerella spp are present in 95%–100% of cases; Gardnerella vaginalis has been found to be more virulent than other BV-associated bacteria (BVAB) in vitro. However, G. vaginalis is found in women with normal vaginal microbiota and colonisation is not sufficient for BV development. We hypothesise that Gardnerella spp initiate BV biofilm formation, but incident BV (iBV) requires incorporation of other key …

Autophagy And Cell Wall Integrity Pathways Coordinately Regulate The Development And Pathogenicity Through Moatg4 Phosphorylation In Magnaporthe Oryzae, Pusheng Guo, Yurong Wang, Jiayun Xu, Zhixiang Yang, Ziqi Zhang, Jinyi Qian, Jiexiong Hu, Ziyi Yin, Leiyun Yang, Muxing Liu, Xinyu Liu, Gang Li, Haifeng Zhang, Ryan Rumsey, Ping Wang, Zhengguang Zhang

School of Medicine Faculty Publications

Autophagy and Cell wall integrity (CWI) signaling are critical stress-responsive processes during fungal infection of host plants. In the rice blast fungus Magnaporthe oryzae, autophagy-related (ATG) proteins phosphorylate CWI kinases to regulate virulence; however, how autophagy interplays with CWI signaling to coordinate such regulation remains unknown. Here, we have identified the phosphorylation of ATG protein MoAtg4 as an important process in the coordination between autophagy and CWI in M. oryzae. The ATG kinase MoAtg1 phosphorylates MoAtg4 to inhibit the deconjugation and recycling of the key ATG protein MoAtg8. At the same time, MoMkk1, a core kinase of CWI, also phosphorylates …

Targeted Repression Of Topa By Crispri Reveals A Critical Function For Balanced Dna Topoisomerase I Activity In The Chlamydia Trachomatis Developmental Cycle, Li Shen, Leiqiong Gao, Abigail R. Swoboda, Scot P. Ouellette

School of Medicine Faculty Publications

Chlamydia trachomatis is an obligate intracellular bacterium that is responsible for the most prevalent bacterial sexually transmitted infection. Changes in DNA topology in this pathogen have been linked to its pathogenicity-associated developmental cycle. Here, evidence is provided that the balanced activity of DNA topoisomerases contributes to controlling Chlamydia developmental processes. Utilizing catalytically inactivated Cas12 (dCas12)-based clustered regularly interspaced short palindromic repeats interference (CRISPRi) technology, we demonstrate targeted knockdown of chromosomal topA transcription in C. trachomatis without detected toxicity of dCas12. Repression of topA impaired the developmental cycle of C. trachomatis mostly through disruption of its differentiation from a replicative form …

Interplay Between Acetylation And Ubiquitination Of Imitation Switch Chromatin Remodeler Isw1 Confers Multidrug Resistance In Cryptococcus Neoformans, Yang Meng, Yue Ni, Zhuoran Li, Tianhang Jiang, Tianshu Sun, Yanjian Li, Xindi Gao, Hailong Li, Chenhao Suo, Chao Li, Sheng Yang, Tian Lan, Guojian Liao, Tongbao Liu, Ping Wang, Chen Ding

School of Medicine Faculty Publications

Cryptococcus neoformans poses a threat to human health, but anticryptococcal therapy is hampered by the emergence of drug resistance, whose underlying mechanisms remain poorly understood. Herein, we discovered that Isw1, an imitation switch chromatin remodeling ATPase, functions as a master modulator of genes responsible for in vivo and in vitro multidrug resistance in C. neoformans. Cells with the disrupted ISW1 gene exhibited profound resistance to multiple antifungal drugs. Mass spectrometry analysis revealed that Isw1 is both acetylated and ubiquitinated, suggesting that an interplay between these two modification events exists to govern Isw1 function. Mutagenesis studies of acetylation and ubiquitination sites …

The Development Of A Rabies Virus-Vectored Vaccine Against Borrelia Burgdorferi, Targeting Bbi39, Shantel Rios, Bibek Bhattachan, Kruthi Vavilikolanu, Chrysoula Kitsou, Utpal Pal, Matthias J. Schnell

Department of Microbiology and Immunology Faculty Papers

Lyme disease (LD) is the most common tick-borne illness in the United States (U.S.), Europe, and Asia. Borrelia burgdorferi, a spirochete bacterium transmitted by the tick vector Ixodes scapularis, causes LD in the U.S. If untreated, Lyme arthritis, heart block, and meningitis can occur. Given the absence of a human Lyme disease vaccine, we developed a vaccine using the rabies virus (RABV) vaccine vector BNSP333 and an outer surface borrelial protein, BBI39. BBI39 was previously utilized as a recombinant protein vaccine and was protective in challenge experiments; therefore, we decided to utilize this protective antigen in a rabies virus-vectored vaccine …

Genital Tract Infections, The Vaginal Microbiome And Gestational Age At Birth Among Pregnant Women In South Africa: A Cohort Study Protocol, Ranjana M.S. Gigi, Mandisa M. Mdingi, Hyunsul Jung, Shantelle Claassen-Weitz, Lukas Bütikofer, Jeffrey D. Klausner, Christina A. Muzny, Christopher M. Taylor, Janneke H.H.M. Van De Wijgert, Remco P.H. Peters, Nicola Low

School of Medicine Faculty Publications

Introduction Preterm birth complications are the most common cause of death in children under 5 years. The presence of multiple microorganisms and genital tract inflammation could be the common mechanism driving early onset of labour. South Africa has high levels of preterm birth, genital tract infections and HIV infection among pregnant women. We plan to investigate associations between the presence of multiple lower genital tract microorganisms in pregnancy and gestational age at birth. Methods and analysis This cohort study enrols around 600 pregnant women at one public healthcare facility in East London, South Africa. Eligible women are ≥18 years and …

Treatment Response Of Gingival Squamous-Cell Carcinoma To Palliative Intent Immunotherapy, Natalia Trehan, Angelina Debbas, Mykaihla Sternick, Jennifer Johnson, James Gates

Department of Medical Oncology Faculty Papers

The use of PD-1 immune checkpoint inhibitor medications has become a common practice in the treatment of recurrent and metastatic head and neck squamous-cell carcinomas. Success in this setting has led to the investigation of their efficacy in locally advanced cases as a part of first-line therapy. In this report, we detail the treatment response to palliative intent immunotherapy of three geriatric patients with mandibular gingival squamous-cell carcinoma who decided against surgical intervention. Patient #1 was treated with pembrolizumab, a PD-1 inhibitor, and displayed complete clinical and radiologic response of the gingival mass after three months of treatment, which is …

Association Of Chlamydia Trachomatis Burden With The Vaginal Microbiota, Bacterial Vaginosis, And Metronidazole Treatment, Caleb M. Ardizzone, Christopher M. Taylor, Evelyn Toh, Rebecca A. Lillis, Jacob H. Elnaggar, John W. Lammons, Patricia Dehon Mott, Emily L. Duffy, Li Shen, Alison J. Quayle

School of Graduate Studies Faculty Publications

Bacterial vaginosis (BV), a dysbiosis of the vaginal microbiota, is a common coinfection with Chlamydia trachomatis (Ct), and BV-associated bacteria (BVAB) and their products have been implicated in aiding Ct evade natural immunity. Here, we determined if a non-optimal vaginal microbiota was associated with a higher genital Ct burden and if metronidazole, a standard treatment for BV, would reduce Ct burden or aid in natural clearance of Ct infection. Cervicovaginal samples were collected from women at enrollment and, if testing positive for Ct infection, at a follow-up visit approximately one week later. Cervical Ct burden was assessed by inclusion forming …

Re: Incidence Of Sars-Cov-2 Breakthrough Infections After Vaccination In Adults: A Population-Based Survey Through 1 March 2023, Stacia M Desantis, Ashraf Yaseen, Tianyao Hao, Luis León-Novelo, Yashar Talebi, Melissa A Valerio-Shewmaker, Cesar L Pinzon Gomez, Sarah E Messiah, Harold W Kohl, Steven H Kelder, Jessica A Ross, Lindsay N Padilla, Mark Silberman, Samantha Wylie, David Lakey, Jennifer A Shuford, Stephen J Pont, Eric Boerwinkle, Michael D Swartz

Journal Articles

No abstract provided.

Tulathromycin Metaphylaxis Increases Nasopharyngeal Isolation Of Multidrug Resistant Mannheimia Haemolytica In Stocker Heifers, William B. Crosby, Brandi B. Karisch, Lari M. Hiott, Lee J. Pinnell, Alexandra Pittman, Jonathan G. Frye, Charlene R. Jackson, John Dustin Loy, William B. Epperson, John Blanton Jr., Sarah F. Capik, Paul S. Morley, Amelia R. Woolums

School of Veterinary and Biomedical Sciences: Faculty Publications

Bovine respiratory disease (BRD) is a leading cause of disease in feedlot and stocker calves with Mannheimia haemolytica (MH) as one of the most common etiologies. One of the most effective means of controlling BRD is through metaphylaxis, which involves administering antimicrobials to all animals at high risk of developing BRD. However, increasing prevalence of multidrug resistant (MDR) MH may reduce efficacy of metaphylaxis due to decreased susceptibility to drugs used for metaphylaxis. Primarily, this study aimed to determine the effect of tulathromycin metaphylaxis and subsequent BRD treatment on antimicrobial resistance (AMR) in MH isolated from stocker calves. Secondary objectives …

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 …

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 …

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* …

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 …

Additive Effects Of Cyclic Peptide [R4w4] When Added Alongside Azithromycin And Rifampicin Against Mycobacterium Avium Infection, Melissa Kelley, Kayvan Sasaninia, Arbi Abnousian, Ali Badaoui, James Owens, Abrianna Beever, Nala Kachour, Rakesh Kumar Tiwari, Vishwanath Venketaraman

Pharmacy Faculty Articles and Research

Mycobacterium avium (M. avium), a type of nontuberculous mycobacteria (NTM), poses a risk for pulmonary infections and disseminated infections in immunocompromised individuals. Conventional treatment consists of a 12-month regimen of the first-line antibiotics rifampicin and azithromycin. However, the treatment duration and low antibiotic tolerability present challenges in the treatment of M. avium infection. Furthermore, the emergence of multidrug-resistant mycobacterium strains prompts a need for novel treatments against M. avium infection. This study aims to test the efficacy of a novel antimicrobial peptide, cyclic [R4W4], alongside the first-line antibiotics azithromycin and rifampicin in reducing M. avium survival. Colony-forming unit (CFU) …

Nivolumab And Ipilimumab In Combination With Radiotherapy In Patients With High-Risk Locally Advanced Squamous Cell Carcinoma Of The Head And Neck., Jennifer Johnson, Ioannis A. Vathiotis, Larry Harshyne, Ayesha Ali, Voichita Bar-Ad, Rita S. Axelrod, Emily Lorber, Joseph Curry, David Cognetti, Adam J. Luginbuhl, Madalina Tuluc, Scott W Keith, M.G. Mahoney, Athanassios Argiris

Department of Medical Oncology Faculty Papers

BACKGROUND: The combination of nivolumab and ipilimumab has been approved for the treatment of multiple solid tumors. This was a phase I study investigating definitive radioimmunotherapy (RIT) with nivolumab and ipilimumab for the treatment of locally advanced (LA) squamous cell carcinoma of the head and neck (SCCHN).

METHODS: Patients with newly diagnosed, stage IVA-IVB SCCHN eligible for cisplatin-based chemotherapy received nivolumab (3 mg/kg every 2 weeks for a total of 17 doses) and ipilimumab (1 mg/kg every 6 weeks for a total of 6 doses) starting 2 weeks prior to radiotherapy. The primary endpoint was safety of definitive RIT. Secondary …

Preclinical Evaluation Of Anti-Cd38 Therapy In Mature T-Cell Neoplasms, Colleen Isabelle, William Johnson, Kathleen Mcconnell, Ashley Vogel, Jonathan Brammer, Amy Boles, Robyn Keller, Paola Sindaco, Liam Nisenfeld, Guldeep Uppal, Neda Nikbakht, Bruno Calabretta, Patrizia Porazzi, Jerald Gong, Nitin Chakravarti, Pierluigi Porcu, Anjali Mishra

Kimmel Cancer Center Faculty Papers

No abstract provided.

Harnessing Autoimmunity With Dominant Self-Peptide: Modulating The Sustainability Of Tissue-Preferential Antigen-Specific Tregs By Governing The Binding Stability Via Peptide Flanking Residues, Youwei Lin, Shun Sakuraba, Chandirasegaran Massilamany, Jayagopala Reddy, Yoshimasa Tanaka, Sachiko Miyake, Takashi Yamamura

School of Veterinary and Biomedical Sciences: Faculty Publications

Sensitization to self-peptides induces various immunological responses, from autoimmunity to tumor immunity, depending on the peptide sequence; however, the underlying mechanisms remain unclear, and thus, curative therapeutic options considering immunity balance are limited. Herein, two overlapping dominant peptides of myelin proteolipid protein, PLP136-150 and PLP139-151, which induce different forms of experimental autoimmune encephalomyelitis (EAE), monophasic and relapsing EAE, respectively, were investigated. Mice with monophasic EAE exhibited highly resistant to EAE re-induction with any encephalitogenic peptides, whereas mice with relapsing EAE were susceptible, and progressed, to EAE re-induction. This resistance to relapse and reinduction in monophasic EAE mice was associated with …

The Knowns And Unknowns Of Cardiac Autoimmunity In Viral Myocarditis, Kiruthiga Mone, Jay Reddy

School of Veterinary and Biomedical Sciences: Faculty Publications

Myocarditis can result from various infectious and non‐infectious causes that can lead to dilated cardiomyopathy (DCM) and heart failure. Among the infectious causes, viruses are commonly suspected. But the challenge is our inability to demonstrate infectious viral particles during clinical presentations, partly because by that point, the viruses would have damaged the tissues and be cleared by the immune system. Therefore, viral signatures such as viral nucleic acids and virus-reactive antibodies may be the only readouts pointing to viruses as potential primary triggers of DCM. Thus, it becomes hard to explain persistent inflammatory infiltrates that might occur in individuals affected …

Naturally Occurring Highly Pathogenic Avian Influenza Virus H5n1 Clade 2.3.4.4b Infection In Three Domestic Cats In North America During 2023, Sarah J. Sillman, Mary Drozd, Duan S. Loy, Seth P. Harris

School of Veterinary and Biomedical Sciences: Faculty Publications

The Eurasian strain of highly pathogenic avian influenza (HPAI) H5N1 is a devastating pathogen for birds that also has the capacity to infect mammals. This report describes the presentation, clinical case findings (including haemogram and serum biochemistry), gross and microscopic lesions and virus detection in three HPAI H5N1-infected domestic cats from the USA in 2023. All three cats presented with neurological abnormalities and were euthanized due to a poor prognosis within 2 days (two cats) or 10 days (one cat) of known clinical disease onset. Necropsy consistently revealed pulmonary congestion and oedema, and cerebrocortical malacia with haemorrhage was also seen …

Clonal Hematopoiesis Is Associated With Protection From Alzheimer's Disease, Hind Bouzid, Julia A Belk, Max Jan, Yanyan Qi, Chloé Sarnowski, Sara Wirth, Lisa Ma, Matthew R Chrostek, Herra Ahmad, Daniel Nachun, Winnie Yao, Alexa Beiser, Alexander G Bick, Joshua C Bis, Myriam Fornage, William T Longstreth, Oscar L Lopez, Pradeep Natarajan, Bruce M Psaty, Claudia L Satizabal, Joshua Weinstock, Eric B Larson, Paul K Crane, C Dirk Keene, Sudha Seshadri, Ansuman T Satpathy, Thomas J Montine, Siddhartha Jaiswal

Journal Articles

Clonal hematopoiesis of indeterminate potential (CHIP) is a premalignant expansion of mutated hematopoietic stem cells. As CHIP-associated mutations are known to alter the development and function of myeloid cells, we hypothesized that CHIP may also be associated with the risk of Alzheimer's disease (AD), a disease in which brain-resident myeloid cells are thought to have a major role. To perform association tests between CHIP and AD dementia, we analyzed blood DNA sequencing data from 1,362 individuals with AD and 4,368 individuals without AD. Individuals with CHIP had a lower risk of AD dementia (meta-analysis odds ratio (OR) = 0.64, P …

Quantitative Risk Assessment Of Oocyst Versus Bradyzoite Foodborne Transmission Of Toxoplasma Gondii In Brazil, Sophie Zhu, Elizabeth Vanwormer, Beatriz Martínez-López, Lílian Maria Garcia Bahia-Oliveira, Renato Augusto Damatta, Pedro Souto Rodrigues, Karen Shapiro

School of Veterinary and Biomedical Sciences: Faculty Publications

Toxoplasma gondii is a globally distributed zoonotic protozoan parasite. Infection with T. gondii can cause congenital toxoplasmosis in developing fetuses and acute outbreaks in the general population, and the disease burden is especially high in South America. Prior studies found that the environmental stage of T. gondii, oocysts, is an important source of infection in Brazil; however, no studies have quantified this risk relative to other parasite stages. We developed a Bayesian quantitative risk assessment (QRA) to estimate the relative attribution of the two primary parasite stages (bradyzoite and oocyst) that can be transmitted in foods to people in …