Immunology and Infectious Disease Commons^™

A Diverse And Inclusive Academic Membership For All, Victor Puac-Polanco, Alfredo Morabia

Publications and Research

With the growing recognition that diversity and inclusion are essential for the improvement of science and innovation, this commentary provides some perspectives on three findings in the DeVilbiss et al. (2020)'s article and provide points of discussion on factors and strategies to consider when drafting diversity and inclusion programs for the Society for Epidemiologic Research.

Mutational Analysis And Domain Characterization Of The Apolipoprotein L-1 Ion Channel, Charles M. Schaub

Dissertations, Theses, and Capstone Projects

The human innate immunity factor Apolipoprotein L-1 (APOL1) protects against Trypanosoma brucei brucei infection. Recent studies have shown recombinant APOL1 (rAPOL1) inserts into planar lipid bilayers at an acidic pH 5.6 and forms a cation-selective channel, which opens upon subsequent neutralization, pH 7.2. This corresponds with the pH changes APOL1 would encounter during endosome recycling, suggesting that APOL1 forms a pH-gated ion channel in the plasma membrane of the parasite, leading to uncontrolled ion flux and osmotic imbalance. However, structural and domain characteristics of the APOL1 channel are poorly understood, despite potential similarities to diphtheria and colicin toxins. Utilizing E. …

Lps, A Tlr-4 Agonist And Viper A Tlr-4 Inhibitor Upregulate Phagocytosis Of Zymosan In Bv2 Cells, Sherouk Alzeory

Dissertations and Theses

Microglia cells are the first line of innate immunity defense in the central nervous system (CNS). They play a critical role in maintaining CNS homeostasis by having an active but yet balanced phagocytic activity. However, in various CNS related diseases, microglia cells have been shown to malfunction. In Alzheimer's Disease (AD), hyperactive microglia with impaired phagocytic activity is the main hallmark of this disease, along with the accumulation of amyloid-beta aggregates. Additionally, emerging new studies have suggested a fungal infection etiology to AD, specifically in relation to Candida albicans (C.albicans). Thus, understanding the mechanism of fungal clearance in the …

From The Human To The Planetary: Speculative Futures Of Care, Miriam Ticktin

Publications and Research

This is largely a theoretical, speculative essay that takes on the question of what ‘care’ looks like at a moment when climate change is increasingly taking center stage in public and political discussions. Starting with two new practices, namely, humanitarian care for nonhumans and One Health collaborations, I seek to determine what forms of political care can incorporate the well-being of future generations and future iterations of the earth. After an exploration of One Health as an approach to planetary care, I ask what its parts enable us to think, despite its limitations; I focus on the new human-nonhuman assemblages …

Innate Antibodies, Murine Models, And Evolution: A Study Of Trypanosome Lytic Factor Functions And Their Translational Applications, Joseph P. Verdi

Dissertations, Theses, and Capstone Projects

Trypanosome lytic factors (TLFs) are primate-specific antimicrobial protein complexes that lyse African trypanosome parasites by delivering the channel-forming toxin APOL1 to the invading microorganisms. Human serum contains two TLFs that are delivered to the parasite by separate mechanisms, only one of which has been characterized. TLF1 is endocytosed by a receptor that is typically blocked by other serum factors in vivo, suggesting that TLF2 is the more relevant lytic factor in the context of trypanosome immunity. TLF2 is non-covalently associated with polyclonal immunoglobulin M (IgM) antibodies, which we report here to be involved in the uptake mechanism. The TLF2-IgMs …

Endothelial Iqgap1 Regulates Leukocyte Transmigration By Directing The Lbrc To The Site Of Diapedesis, David P. Sullivan, Prarthana J. Dalal, Fanny Jaulin, David B. Sacks, Geri Kreitzer, William A. Muller

Publications and Research

Transendothelial migration (TEM) of leukocytes across the endothelium is critical for inflammation. In the endothelium, TEM requires the coordination of membrane movements and cytoskeletal interactions, including, prominently, recruitment of the lateral border recycling compartment (LBRC). The scaffold protein IQGAP1 was recently identified in a screen for LBRC-interacting proteins. Knockdown of endothelial IQGAP1 disrupted the directed movement of the LBRC and substantially reduced leukocyte TEM. Expression of truncated IQGAP1 constructs demonstrated that the calponin homology domain is required for IQGAP1 localization to endothelial borders and that the IQ domain, on the same IQGAP1 polypeptide, is required for its function in TEM. …

Synthesis And Evaluations Of “1,4-Triazolyl Combretacoumarins” And Desmethoxy Analogs, Tashrique A. Khandaker, Jessica D. Hess, Renato Aguilera, Graciela Andrei, Robert Snoeck, Dominique Schols, Padmanava Pradhan, Mahesh K. Lakshman

Publications and Research

1,4-Triazolyl combretacoumarins have been prepared by linking the trimethoxyarene unit of combretastatin A4 with coumarins, via a 1,2,3-triazole. For this, 4-azidocoumarins were accessed by a sequential two-step, one-pot reaction of 4-hydroxycoumarins with (benzotriazol-1-yloxy)tris(dimethylamino)phosphonium hexafluorophosphate (BOP), followed by reaction with NaN₃. In the reaction with BOP, a coumarin-derived phosphonium ion intermediate seems to form, leading to an O⁴-(benzotriazolyl)coumarin derivative. For the CuAAC reaction of azidocoumarins with 5-ethynyl-1,2,3-trimethoxybenzene, catalytic [(MeCN)₄Cu]PF₆ in CH₂Cl₂/MeOH with 2,6-lutidine, at 50 ^oC, was suitable. The 4-azidocoumarins were less reactive as compared to PhN₃ and …

Observation Of Visitors At A Chimpanzee (Pan Troglodytes Schweinfurthii) Ecotourism Site Reveals Opportunity For Multiple Modes Of Pathogen Transmission, Darcey Glasser

Theses and Dissertations

Chimpanzee (Pan troglodytes) tracking is a popular ecotourism activity across Sub-Saharan Africa, offering visitors a personal wildlife experience. However, chimpanzee ecotourism may increase the risk of disease transmission between chimpanzees and people. This study assessed how tourist behaviors might facilitate cross-species disease transmission in Kibale National Park, Uganda.

Abrogation Of Endogenous Glycolipid Antigen Presentation On Myelin-Laden Macrophages By D-Sphingosine Ameliorates The Pathogenesis Of Experimental Autoimmune Encephalomyelitis, Yi Ban, Wenjuan Dong, Lixing Zhang, Tian Zhou, Ahmad Sabri Altiti, Khaleel Ali, David R. Mootoo, Victoria A. Biaho, Timothy Hla, Yi Ren, Xiaojing Ma

Publications and Research

Background: Although myelin is composed of mostly lipids, the pathological role of myelin lipids in demyelinating diseases remains elusive. The principal lipid of the myelin sheath is b-galactosylceramide (b-Galcer). Its a-anomer (a-Galcer) has been demonstrated to be antigenically presented by macrophages via CD1d, a MHC class I-like molecule. Myelin, which is mostly composed of b-Galcer, has been long considered as an immunologically-inert neuron insulator, because the antigen-binding cleft of CD1d is highly a-form-restricted.

Results: Here, we report that CD1d-mediated antigenic presentation of myelin-derived galactosylceramide (Mye-GalCer) by macrophages contributed significantly to the progression of experimental autoimmune encephalomyelitis (EAE). Surprisingly, this presentation …

Characterization Of Immunomodulatory Microbial Factors In Medicinal Plants, Kriti Kalpana

Dissertations, Theses, and Capstone Projects

Medicinal plants are one of the biggest sources of natural products with therapeutic importance. There are currently over 28,000 plants with putative medicinal values. Plant-derived compounds have been explored extensively for various biological activities ranging from anti-cancer, immune-boosting to anti-inflammatory and anti-oxidant. Some of the most important therapeutic agents are of plant-origin, such as paclitaxel from Pacific yew (Taxus brevifolia) and artemisinin from qinghao su (a Chinese medicinal herb; a.k.a. Artemisia annua) to name a few.

The study presented in this thesis started out as classical pharmacognosy research, which focused on the identification of immunostimulatory factors in …

Characterizing Chromosomal Aberrations In Cells Deficient For Both Atm And Msh2, Yeliz Inalman

Dissertations and Theses

Ataxia telangiectasia mutated (ATM) and mutS homologue 2 (MSH2) are important DNA repair proteins that participate in DNA repair pathways to maintain genomic integrity. Mice deficient for ATM and MSH2 mice are viable. However, ATM^-/- mice show growth retardation, neurological defects, and spontaneous lymphomagenesis. MSH2^-/- mice suffer from aggressive lymphoid tumors between two to five months of age and have increased microsatellite instability, which predisposes MSH2^-/- mice to carcinomas. However, mice deficient in both ATM and MSH2 are unable to survive beyond postnatal day 21 (P21). The observed lethality in ATM^-/-MSH2^-/- mice may result …

Instances Of Influenza In The United States Visualized, Parth Patel

Publications and Research

The Tycho Project collects large data sets related to healthcare and in particular, instances and geographical information of diseases. We look at the instance counts and locations of Influenza from 1919-1951 across the United States. We hope to find seasonal and geographical insight to the spread of the disease.

Strategies Involving The Food-Derived Agent Curcumin To Eliminate Brain Cancer, Sumit Mukherjee

Dissertations, Theses, and Capstone Projects

Glioblastoma (GBM) is one of the most deadly forms of cancer with a mean 5-year survival rate of ≤5%. We have used the non-invasive strategy of long-term intranasal (IN) delivery of a glioblastoma-directed adduct of curcumin (CC), CC-CD68Ab, into the brain of murine GBM cell line GL261-implanted mice to study the therapeutic effect of CC on GBM remission. The treatment caused GBM tumor remission in 50% of GL261-implanted GBM mice. A similar rescue rate (60%) was also achieved through long-term intraperitoneal (i.p) infusion of a highly bioavailable phosphotidylcholine (PC)-encapsulated formulation of CC, Curcumin Phytosome Meriva (CCP), into the GL261-implanted GBM …

Evidence For Organelle-Like Extracellular Vesicles From A Parasite Of Drosophila And Their Function In Suppressing Host Immunity, Mary Heavner

Dissertations, Theses, and Capstone Projects

Parasitic wasps act as keystone species in natural ecosystems. Adept at suppressing immunity of their insect hosts, these natural enemies of insect pests are used for biocontrol in many parts of the world. Female parasitic wasps of the closely-related species Leptopilina heterotoma (Lh), a generalist of many Drosophilia flies, and Leptopilina boulardi (Lb), a specialist on flies of the melanogaster subgroup, produce venom and virus-like particles (VLPs) in their long gland-reservoir complexes, a secretory organ connected to ovipositors. Venom and VLPs are deposited, along with wasp eggs, into the body of the wasp’s larval fly host …

Generating And Repairing Genetically Programmed Dna Breaks During Immunoglobulin Class Switch Recombination, Laura Nicolas, Montserrat Cols, Jee Eun Choi, Jayanta Chaudhuri

Publications and Research

Adaptive immune responses require the generation of a diverse repertoire of immunoglobulins (Igs) that can recognize and neutralize a seemingly infinite number of antigens. V(D)J recombination creates the primary Ig repertoire, which subsequently is modified by somatic hypermutation (SHM) and class switch recombination (CSR). SHM promotes Ig affinity maturation whereas CSR alters the effector function of the Ig. Both SHM and CSR require activation-induced cytidine deaminase (AID) to produce dU:dG mismatches in the Ig locus that are transformed into untemplated mutations in variable coding segments during SHM or DNA double-strand breaks (DSBs) in switch regions during CSR. Within the Ig …

Strains Of Bacterial Species Induce A Greatly Varied Acute Adaptive Immune Response: The Contribution Of The Accessory Genome, Uri Sela, Chad W. Euler, Joel Correa Da Rosa, Vincent A. Fischetti

Publications and Research

A fundamental question in human susceptibility to bacterial infections is to what extent variability is a function of differences in the pathogen species or in individual humans. To focus on the pathogen species, we compared in the same individual the human adaptive T and B cell immune response to multiple strains of two major human pathogens, Staphylococcus aureus and Streptococcus pyogenes. We found wide variability in the acute adaptive immune response induced by various strains of a species, with a unique combination of activation within the two arms of the adaptive response. Further, this was also accompanied by a dramatic …

Flp-1 Neuropeptides Modulate Sensory And Motor Circuits In The Nematode Caenorhabditis Elegans, Ingrid Buntschuh, Daniel A. Raps, Ivor Joseph, Christopher Reid, Alexander Chait, Raubern Totanes, Michelle Sawh, Chris Li

Publications and Research

Parasitic nematodes infect over one quarter of the population worldwide, causing morbidity in over one billion people. Current anthelmintic drugs are beginning to lose effectiveness due to the presence of resistant strains. We are interested in the role of neuropeptides, which regulate behaviors in all organisms, as another possible target for anthelmintic drugs. FMRFamide-related peptides (FaRPs) are a family of neuropeptides that are conserved throughout the animal kingdom. In particular, nematodes contain the largest family of FaRPs identified thus far and many of these FaRPs are identical among different nematode species; FaRPs in nematodes are collectively referred to as FLPs …

Quantification Of Hiv-1 Rna Among Men Who Have Sex With Men Using An At-Home Self-Collected Dried Blood Spot Specimen: Feasibility Study, Sabina Hirshfield, Richard A. Teran, Martin J. Downing Jr., Mary Ann Chiasson, Hong-Van Tieu, Laura Dize, Charlotte A. Gaydos

Publications and Research

Background: Suboptimal antiretroviral therapy (ART) adherence and disengagement in care present significant public health challenges because of the increased probability of HIV transmission. In the United States, men who have sex with men (MSM) continue to be disproportionately affected by HIV, highlighting a critical need to engage high-risk MSM living with HIV who are not engaged or retained in care.

Objective: The aim of the study was to assess the feasibility of at-home blood self-collection and laboratory quantification of HIV-1 RNA viral load (VL) to report laboratory-based VL outcomes and compare self-reported and laboratory-reported VL

Methods: Between 2016 and 2017, …

Bone Marrow Derived Progenitor Cells And Their Contributions To The Thymic Stroma, Mohammed Hoque

Dissertations and Theses

The thymus serves as the primary lymphoid organ responsible for the development and selection of a self-tolerant T cell repertoire. In paradox to its critical functions for the adaptive immune response, the thymus undergoes a profound age associated decline beginning in early adult life resulting in significant decline in T-cell function.Thymic epithelial cells (TECs) are the most critical component of the thymic microenvironment and undergo rapid turn-over, so understanding the cellular mechanisms responsible for the maintenance of TEC number and organization will be critical in counteracting age associated involution, particularly in cancer patients, due to enhanced degeneration in response to …

Nlrp10 Enhances Cd4+ T-Cell-Mediated Ifnγ Response Via Regulation Of Dendritic Cell-Derived Il-12 Release, Maurizio Vacca, Julia Böhme, Lisa Zambetti, Hanif Javanmard Khameneh, Bhairav S. Paleja, Federica Laudisi, Adrian W. S. Ho, Kurt Neo, Keith Weng Kit Leong, Mardiana Marzuki, Bernett Lee, Michael Poidinger, Laura Santambrogio, Liana Tsenova, Francesca Zolezzi, Gennaro De Libero, Amit Singhal, Alessandra Mortellaro

Publications and Research

NLRP10 is a nucleotide-binding oligomerization domain-like receptor that functions as an intracellular pattern recognition receptor for microbial products. Here, we generated a Nlrp10−/− mouse to delineate the role of NLRP10 in the host immune response and found that Nlrp10−/− dendritic cells (DCs) elicited sub-optimal IFNγ production by antigenspecific CD4+ T cells compared to wild-type (WT) DCs. In response to T-cell encounter, CD40 ligation or Toll-like receptor 9 stimulation, Nlrp10−/− DCs produced low levels of IL-12, due to a substantial decrease in NF-κB activation. Defective IL-12 production was also evident in vivo and affected IFNγ production by CD4+ T cells. Upon …

Trypanosome Lytic Factor Mediated Immunity Against Leishmania Sp., Jyoti Pant

Dissertations, Theses, and Capstone Projects

Trypanosome Lytic Factor (TLF) is an innate immunity complex that was originally discovered to protect against African Trypanosomes. The major components of TLF are Apolipoprotein A1 (APOA1), Apolipoprotein L1 (APOL1) and HPR (Haptoglobin Related Protein), where APOL1 is necessary and sufficient for trypanolysis. Recently we have shown that TLF ameliorates infections by cutaneous Leishmania species. Here we investigated the effect of different primate and human TLF against different Leishmania sp. Our result shows that TLF kills metacyclic promastigotes of cutaneous Leishmania sp. within immune cells such as neutrophils and macrophages by two different mechanism. Using transiently transfected and germline transgenic …

Zika Virus-Like Particle (Vlp) Based Vaccine, Héléne Boigard, Alexandra Alimova, George R. Martin, Al Katz, Paul Gottlieb, Jose M. Galarza

Publications and Research

The newly emerged mosquito-borne Zika virus poses a major public challenge due to its ability to cause significant birth defects and neurological disorders. The impact of sexual transmission is unclear but raises further concerns about virus dissemination. No specific treatment or vaccine is currently available, thus the development of a safe and effective vaccine is paramount. Here we describe a novel strategy to assemble Zika virus-like particles (VLPs) by co-expressing the structural (CprME) and non-structural (NS2B/NS3) proteins, and demonstrate their effectiveness as vaccines. VLPs are produced in a suspension culture of mammalian cells and self-assembled into particles closely resembling Zika …

Demographic Transition And The Dynamics Of Measles In Six Provinces In China: A Modeling Study, Sheng Li, Chao Ma, Lixin Hao, Qiru Su, Zhijie An, Fubao Ma, Shuyun Xie, Aiqiang Xu, Yangyang Zhang, Zhengrong Ding, Hui Li, Lisa Cairns, Huaqing Wang, Huiming Luo, Ning Wang, Li Li, Matthew J. Ferrari

Publications and Research

Background Industrialization and demographic transition generate nonstationary dynamics in human populations that can affect the transmission and persistence of infectious diseases. Decades of increasing vaccination and development have led to dramatic declines in the global burden of measles, but the virus remains persistent in much of the world. Here we show that a combination of demographic transition, as a result of declining birth rates, and reduced measles prevalence, due to improved vaccination, has shifted the age distribution of susceptibility to measles throughout China.

Methods and findings We fit a novel time-varying catalytic model to three decades of age-specific measles case …

Why We Still Need To Worry About Bees, Meaghan Lee Callaghan

Capstones

American honey bees, and other native bee species, are still in decline, though the specter of colony collapse disorder may be fading behind us. Colony decline, the loss of bees overwinter experienced across the country at a quarter to third lost per hive (sometimes more), is now expected. Losses can include those from colony collapse disorder. The author discusses the different causes for colony decline and speaks to bee health scientists and local beekeepers. Read more at: http://www.meaghanleecallaghan.com/capstone/index.html

Ifn-G Induces Histone 3 Lysine 27 Trimethylation In A Small Subset Of Promoters To Stably Silence Gene Expression In Human Macrophages, Yu Qiao, Kyuho Kang, Eugenia Giannopoulou, Celeste Fang, Lionel B. Ivashkiv

Publications and Research

The mechanisms by which IFN-g activates expression of interferon-stimulated genes that have inflammatory and host defense functions are well understood. In contrast, little is known about how IFN-g represses gene expression. By using transcriptomic and epigenomic analysis, we found that stable repression of a small group of genes by IFN-g is associated with recruitment of the histone methyltransferase EZH2 and deposition of the negative mark histone 3 lysine 27 trimethylation (H3K27me3) at their promoters. Repressed genes included MERTK, PPARG, and RANK, which have anti-inflammatory functions and promote osteoclast differentiation. Gene repression and H3K27me3 persisted after IFN-g signaling was terminated, and …

Receptor-Type Guanylyl Cyclase At 76c (Gyc76c) Regulates De Novo Lumen Formation During Drosophila Tracheal Development, Monn Monn Myat, Unisha Patel

Publications and Research

Lumen formation and maintenance are important for the development and function of essential organs such as the lung, kidney and vasculature. In the Drosophila embryonic trachea, lumena formde novo to connect the different tracheal branches into an interconnected network of tubes. Here, we identify a novel role for the receptor type guanylyl cyclase at 76C (Gyc76C) in de novo lumen formation in the Drosophila trachea.We show that in embryosmutant for gyc76C or its downsteam effector protein kinase G (PKG) 1, tracheal lumena are disconnected. Dorsal trunk (DT) cells of gyc76C mutant embryos migrate to contact each other and complete the …

Pharmacologic Inhibition Of Host Phosphodiesterase-4 Improves Isoniazid-Mediated Clearance Of Mycobacterium Tuberculosis, Selvakumar Subbian, Mi-Sun Koo, Liana Tsenova, Vikram Khetani, Jerome B. Zeldis, Dorothy Fallows, Gilla Kaplan

Publications and Research

The lengthy duration of multidrug therapy needed to cure tuberculosis (TB) poses significant challenges for global control of the disease. Moreover, chronic inflammation associated with TB leads to pulmonary damage that can remain even after successful cure. Thus, there is a great need for the development of effective shorter drug regimens to improve clinical outcome and strengthen TB control. Host-directed therapy (HDT) is emerging as a novel adjunctive strategy to enhance the efficacy and shorten the duration of TB treatment. Previously, we showed that the administration of CC-3052, a phosphodiesterase-4 inhibitor (PDE4i), reduced the host inflammatory response during Mycobacterium tuberculosis …

P2x7r-Panx1 Complex Impairs Bone Mechanosignaling Under High Glucose Levels Associated With Type-1 Diabetes, Zeynep Seref-Ferlengez, Stephanie Maung, Mitchell B. Schaffler, David C. Spray, Sylvia O. Suadicani, Mia M. Thi

Publications and Research

Type 1 diabetes (T1D) causes a range of skeletal problems, including reduced bone density and increased risk for bone fractures. However, mechanisms underlying skeletal complications in diabetes are still not well understood.We hypothesize that high glucose levels in T1D alters expression and function of purinergic receptors (P2Rs) and pannexin 1 (Panx1) channels, and thereby impairs ATP signaling that is essential for proper bone response to mechanical loading and maintenance of skeletal integrity. We first established a key role for P2X7 receptor-Panx1 in osteocyte mechanosignaling by showing that these proteins are co-expressed to provide a major pathway for flow-induced ATP release. …

Killer-Cell Immunoglobulin-Like Receptor (Kir) Gene Profiles Modify Hiv Disease Course, Not Hiv Acquisition In South African Women, V. Naranbhai, D. De Assis Rosa, L. Werner, R. Moodley, H. Hong, A. Kharsany, K. Mlisana, S. Sibeko, N. Garrett, D. Chopera, William H. Carr, Q. Abdool Karim, A. V. S. Hill, S. S. Abdool Karim, M. Altfeld, C. M. Gray, T. Ndung’U

Publications and Research

Background: Killer-cell Immunoglobulin-like Receptors(KIR) interact with Human Leukocyte Antigen(HLA) to modify natural killer- and T-cell function. KIR are implicated in HIV acquisition by small studies that have not been widely replicated. A role for KIR in HIV disease progression is more widely replicated and supported by functional studies.

Methods: To assess the role of KIR and KIR ligands in HIV acquisition and disease course, we studied at-risk women in South Africa between 2004–2010. Logistic regression was used for nested case–control analysis of 154 women who acquired vs. 155 who did not acquire HIV, despite high exposure. Linear mixed-effects models were …

An Evolutionary Vaccination Game In The Modified Activity Driven Network By Considering The Closeness, Dun Han, Mei Sun

Publications and Research

In this paper, we explore an evolutionary vaccination game in the modified activity driven network by considering the closeness. We set a closeness parameter p which is used to describe the way of connection between two individuals. The simulation results show that the closeness p may have an active role in weakening both the spreading of epidemic and the vaccination. Besides, when vaccination is not allowed, the final recovered density increases with the value of the ratio of the infection rate to the recovery rate λ/μ. However, when vaccination is allowed the final density of recovered individual first increases and …