Medical Immunology Commons^™

Loss Of H2r Signaling Disrupts Neutrophil Homeostasis And Promotes Inflammation-Associated Colonic Tumorigenesis In Mice, Zhongcheng Shi, Yuko Mori-Akiyama, Wa Du, Robert Fultz, Yanling Zhao, Wenly Ruan, Susan Venable, Melinda A Engevik, James Versalovic

Faculty, Staff and Students Publications

BACKGROUND & AIMS: We previously showed that histamine suppressed inflammation-associated colonic tumorigenesis through histamine type 2 receptor (H2R) signaling in mice. This study aimed to precisely elucidate the downstream effects of H2R activation in innate immune cells.

METHODS: Analyses using online databases of single-cell RNA sequencing of intestinal epithelial cells in mice and RNA sequencing of mouse immune cells were performed to determine the relative abundances of 4 histamine receptors among different cell types. Mouse neutrophils, which expressed greater amounts of H2R, were collected from the peritoneum of wild-type and H2R-deficient mice, of which low-density and high-density neutrophils were extracted …

Stat6 Suppression Prevents Bleomycin-Induced Dermal Fibrosis, Hua Sun, Ashish Damania, Megan L Mair, Eniola Otukoya, Yi-Dong Li, Katherine Polsky, Yuying Zeng, Jeremiah A Alt, Martin J Citardi, David B Corry, Amber U Luong, John Morgan Knight

Faculty, Staff and Student Publications

Unified airway disease, including concurrent asthma and chronic rhinosinusitis (CRS), is a common, but poorly understood disorder with no curative treatment options. To establish a murine model of chronic unified eosinophilic airway inflammation, mice were challenged with Aspergillus niger, and sinonasal mucosa and lung tissue were evaluated by immunohistochemistry, flow cytometry, and gene expression. Inhalation of A niger conidia resulted in a Th2-biased lung and sinus inflammation that typifies allergic asthma and CRS. Gene network and pathway analysis correlated with human disease with upregulation of not only the JAK-STAT and helper T-cell pathways, but also less expected pathways governing …

Pathologic Inflammation In Malnutrition Is Driven By Proinflammatory Intestinal Microbiota, Large Intestine Barrier Dysfunction, And Translocation Of Bacterial Lipopolysaccharide, Grace T Patterson, Elvia Y Osorio, Alex Peniche, Sara M Dann, Erika Cordova, Geoffrey A Preidis, Ji Ho Suh, Ichiaki Ito, Omar A Saldarriaga, Michael Loeffelholz, Nadim J Ajami, Bruno L Travi, Peter C Melby

Faculty, Staff and Students Publications

Acute malnutrition, or wasting, is implicated in over half of all deaths in children under five and increases risk of infectious disease. Studies in humans and preclinical models have demonstrated that malnutrition is linked to an immature intestinal microbiota characterized by increased prevalence of Enterobacteriaceae. Observational studies in children with moderate acute malnutrition (MAM) have also observed heightened systemic inflammation and increased circulating bacterial lipopolysaccharides (LPS; endotoxin). However, the mechanisms that underpin the systemic inflammatory state and endotoxemia, and their pathophysiological consequences, remain uncertain. Understanding these pathophysiological mechanisms is necessary to design targeted treatments that will improve the unacceptable rate …

Monoclonal Antibodies Protect Aged Rhesus Macaques From Sars-Cov-2-Induced Immune Activation And Neuroinflammation, Anil Verma, Chase E. Hawes, Yashavanth Shaan Lakshmanappa, Jamin W. Roh, Brian A. Schmidt, Joseph Dutra, William Louie, Hongwei Liu, Zhong Min Ma, Jennifer K. Watanabe, Jodie L. Usachenko, Ramya Immareddy, Rebecca L. Sammak, Rachel Pollard, J. Rachel Reader, Katherine J. Olstad, Lark L. Coffey, Pamela A. Kozlowski, Dennis J. Hartigan-O'Connor, Michel Nussenzweig

School of Graduate Studies Faculty Publications

Anti-viral monoclonal antibody (mAb) treatments may provide immediate but short-term immunity from coronavirus disease 2019 (COVID-19) in high-risk populations, such as people with diabetes and the elderly; however, data on their efficacy in these populations are limited. We demonstrate that prophylactic mAb treatment blocks viral replication in both the upper and lower respiratory tracts in aged, type 2 diabetic rhesus macaques. mAb infusion dramatically curtails severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2)-mediated stimulation of interferon-induced chemokines and T cell activation, significantly reducing development of interstitial pneumonia. Furthermore, mAb infusion significantly dampens the greater than 3-fold increase in SARS-CoV-2-induced effector CD4 …

Multiple Autonomous Cell Death Suppression Strategies Ensure Cytomegalovirus Fitness, Pratyusha Mandal, Lynsey Nagrani, Liliana Hernandez, Anita Louise Mccormick, Christopher Dillon, Heather Koehler, Linda Roback, Emad S Alnemri, Douglas Green, Edward Mocarski

Department of Biochemistry and Molecular Biology Faculty Papers

Programmed cell death pathways eliminate infected cells and regulate infection-associated inflammation during pathogen invasion. Cytomegaloviruses encode several distinct suppressors that block intrinsic apoptosis, extrinsic apoptosis, and necroptosis, pathways that impact pathogenesis of this ubiquitous herpesvirus. Here, we expanded the understanding of three cell autonomous suppression mechanisms on which murine cytomegalovirus relies: (i) M38.5-encoded viral mitochon-drial inhibitor of apoptosis (vMIA), a BAX suppressor that functions in concert with M41.1-encoded viral inhibitor of BAK oligomerization (vIBO), (ii) M36-encoded viral inhibitor of caspase-8 activation (vICA), and (iii) M45-encoded viral inhibitor of RIP/RHIM activation (vIRA). Following infection of bone marrow-derived macrophages, the virus initially …

Modulation Of Glucose Homeostasis By Nucleotide P2y2 Receptor And Biological Sex, Hailee Anne Marino

Graduate Theses/Dissertations

Recent insights into the pathological role of Nucleotide P2Y₂ receptor suggest P2Y₂R involvement in high fat diet-induced obesity and potentiates insulin resistance. However, these recent insights do not demonstrate how P2Y₂R modulates glucose homeostasis under physiological conditions. Further, it remains unknown how sex biological factors influence P2Y₂R receptor signaling in the regulation of glucose homeostasis. The research objective for the present study is to elucidate the novel roles of P2Y₂ in fasting blood glucose and glucose tolerance (basal insulin sensitivity) under resting conditions in males and females. We expected that under physiological …

Effect Of Lactoferrin To Increase Drug Permeability Of Primary Pulmonary Mycobacterial Granulomas, Thao Nguyen, Thao Kt Nguyen

Dissertations and Theses (Open Access)

Despite extensive research and worldwide eradication efforts, Mycobacterium tuberculosis (Mtb) remains a major infectious pathogen to the human population with about 10 million cases of infection per year globally. The host-pathogen interaction, pulmonary granuloma formation, and Mtb adaptions result in increased complexity of the disease. Granulomas are formed by active immune responses generated during Mtb infection, and serve to contain and limit bacterial dissemination. The major mycobacterial surface mycolic acid, trehalose 6,6'-dimycolate (TDM), functions in multiple ways to enhance immune cell recruitment of sites of infection, to induce inflammation and granulomatous responses, and to initiate survival strategies for …

Sodium Pyruvate Ameliorates Influenza A Virus Infection In Vitro And In Vivo, Jessica M. Reel

Graduate Theses/Dissertations

Pyruvate is produced in duplicate at the end of glycolysis in addition to ATP and NADH. Pyruvate is the metabolite of choice in most cells, whether obtained exogenously or endogenously. Recently we found that the addition of pyruvate’s conjugate base, sodium pyruvate, to cell culture media dampened the immune response to influenza A virus (IAV) infection in cultured innate immune cells. Thus, I decided to investigate the mechanism and potential for treatment of IAV. In vitro using bone marrow derived macrophages that were infected with IAV we found that adding sodium pyruvate to the media decreased immune signaling pathways through …

Suppression Of Inflammation Of Cytokine Following Induced Francisella Tularensis Infection, Nicole Renee Setzu

Open Access Theses & Dissertations

Francisella tularensis is intracellular bacteria which is the causative agent of the disease Tularemia. Highly virulent in both humans and animals, it takes only as few as 10 microorganisms to cause a lethal infection. The bacteria can enter via direct or indirect routes causing the activations of the host innate inflammatory response to ensue. The bacteria invade host dendritic cells and neutrophils but predominately macrophages. This causes a mass inflammatory response resulting in the cytokine storm. Activation of Natural Killer T (NKT) cells has been shown to suppress inflammation in in vivo studies. Development and optimization of an in vitro …

The Effects Of Myelin On Macrophage Activation Are Phenotypic Specific Via Cpla2 In The Context Of Spinal Cord Injury Inflammation, Timothy J. Kopper, Bei Zhang, William M. Bailey, Kara E. Bethel, John C. Gensel

Physiology Faculty Publications

Spinal cord injury (SCI) produces chronic, pro-inflammatory macrophage activation that impairs recovery. The mechanisms driving this chronic inflammation are not well understood. Here, we detail the effects of myelin debris on macrophage physiology and demonstrate a novel, activation state-dependent role for cytosolic phospholipase-A2 (cPLA₂) in myelin-mediated potentiation of pro-inflammatory macrophage activation. We hypothesized that cPLA₂ and myelin debris are key mediators of persistent pro-inflammatory macrophage responses after SCI. To test this, we examined spinal cord tissue 28-days after thoracic contusion SCI in 3-month-old female mice and observed both cPLA₂ activation and intracellular accumulation of lipid-rich myelin …

Immunomodulatory Effects Of Azithromycin Revisited: Potential Applications To Covid-19, Vincent J. Venditto, Dalia Haydar, Ahmed K. Abdel-Latif, John C. Gensel, Michael I. Anstead, Michelle G. Pitts, Jarrod W. Creameans, Timothy J. Kopper, Chi Peng, David J. Feola

Pharmaceutical Sciences Faculty Publications

The rapid advancement of the COVID-19 pandemic has prompted an accelerated pursuit to identify effective therapeutics. Stages of the disease course have been defined by viral burden, lung pathology, and progression through phases of the immune response. Immunological factors including inflammatory cell infiltration and cytokine storm have been associated with severe disease and death. Many immunomodulatory therapies for COVID-19 are currently being investigated, and preliminary results support the premise of targeting the immune response. However, because suppressing immune mechanisms could also impact the clearance of the virus in the early stages of infection, therapeutic success is likely to depend on …

Intrapulmonary Administration Of Purified Neil2 Abrogates Nf-Κb-Mediated Inflammation, Nisha Tapryal, Shandy Shahabi, Anirban Chakraborty, Koa Hosoki, Maki Wakamiya, Gobinda Sarkar, Gulshan Sharma, Victor J Cardenas, Istvan Boldogh, Sanjiv Sur, Gourisankar Ghosh, Tapas K Hazra

Faculty, Staff and Students Publications

Aberrant or constitutive activation of nuclear factor kappa B (NF-κB) contributes to various human inflammatory diseases and malignancies via the upregulation of genes involved in cell proliferation, survival, angiogenesis, inflammation, and metastasis. Thus, inhibition of NF-κB signaling has potential for therapeutic applications in cancer and inflammatory diseases. We reported previously that Nei-like DNA glycosylase 2 (NEIL2), a mammalian DNA glycosylase, is involved in the preferential repair of oxidized DNA bases from the transcriptionally active sequences via the transcription-coupled base excision repair pathway. We have further shown that Neil2-null mice are highly sensitive to tumor necrosis factor α (TNFα)- and lipopolysaccharide-induced …

Reversal Of Neurodegeneration By Engineered Monocytes In Alzheimer’S Disease, Chao-Hsien Chen

Dissertations and Theses (Open Access)

The health challenges posed by Alzheimer’s disease (AD) continue to grow as societies age worldwide. Accumulation of Tau-associated pathology correlates with clinical cognitive deterioration in AD. Resident myeloid cells within the central nervous system (CNS) have a limited capacity to uptake and degrade Tau; however, the resulting secretion of proinflammatory cytokines only acts to accelerate neurodegeneration. Therapeutic antibodies can reduce the neurotoxic oligomeric form of Tau (o-Tau), but in doing so they also aggravate inflammation. Attenuating mutation of the antibody Fc region can silence inflammation but also eliminates its capacity to mediate o-Tau clearance by CNS myeloid cells. Thus, there …

Hdac6 Mediates Macrophage Inos Expression And Excessive Nitric Oxide Production In The Blood During Endotoxemia, Yan Wang, Ke Wang, Jian Fu

Toxicology and Cancer Biology Faculty Publications

Excessive nitric oxide (NO) production and NO-mediated nitrative stress contribute to vascular dysfunction, inflammation, and tissue injury in septic shock. New therapeutic targets are urgently needed to provide better control of NO level during septic shock. In the present study, we investigated the role of HDAC6 in the regulation of NO production and nitrative stress in a mouse model of endotoxin-induced septic shock. HDAC6 deficient mice and a specific HDAC6 inhibitor were utilized in our studies. Our data clearly indicate that HDAC6 is an important mediator of NO production in macrophages. HDAC6 mediates NO production through the regulation of iNOS …

Correlation Of Inflammation In Arthritis With The Myelination In The Brain, Anna Spears

Honors Theses

This study was conducted to investigate whether the influence of arthritis has an effect on the cerebral white matter. The project was performed at the South Oxford Campus, where diffusion tensor imaging (DTI) data was obtained from the Nathan Kline Institute-Rockland Sample (NKI- RS). Image processing was conducted using Functional Magnetic Resonance Imaging of Brain Software Library in which we obtained raw data to formulate Apparent Diffusion Coefficient (ADC), Axial Diffusivity (AD), Radial Diffusivity (RD), and Fractional Anisotropy. A one way Analysis of Covariance (ANCOVA) was performed to determine the significant difference between the history of arthritis on each of …

Insights From Immuno-Oncology: The Society For Immunotherapy Of Cancer Statement On Access To Il-6-Targeting Therapies For Covid-19., Paolo Antonio Ascierto, Bernard Fox, Walter Urba, Ana Carrizosa Anderson, Michael B Atkins, Ernest C Borden, Julie Brahmer, Lisa H Butterfield, Alessandra Cesano, Daniel Chen, Tanja De Gruijl, Robert O Dillman, Charles G Drake, Leisha A Emens, Thomas F Gajewski, James L Gulley, F Stephen Hodi, Patrick Hwu, David Kaufman, Howard Kaufman, Michael Lotze, Douglas G Mcneel, Kim Margolin, Francesco Marincola, Michael J Mastrangelo, Marcela V Maus, David R Parkinson, Pedro J Romero, Paul M Sondel, Stefani Spranger, Mario Sznol, George J Weiner, Jon M Wiggington, Jeffrey S Weber

Department of Microbiology and Immunology Faculty Papers

No abstract provided.

The Interplay Of The Oral-Gut Microbiome With Chronic Inflammation In Rheumatoid Arthritis And Crohn's Disease, Anuradha Rampersaud

Mako: NSU Undergraduate Student Journal

Abstract

Rheumatoid Arthritis (RA) and Crohn’s Disease (CD) are both chronic inflammatory diseases that share developmental and treatment similarities. RA’s symptoms include swelling, stiffness, and pain in synovial joints, corresponding with bone and cartilage destruction. CD’s symptoms include abdominal pain, bowel obstruction, bloating, diarrhea, and fever. The purpose of this literature review was to investigate the links between these two diseases and propose future treatment and prevention targets. Current treatment for RA and CD aims to suppress inflammation by targeting its mediators. However, this review noted that there should be greater focus on resolving inflammation. Both diseases are characterized by …

It's A Hard Nacht Life: Understanding How Nlrp12 Ticks, Abbigale Julia Brown

Graduate Theses/Dissertations

The protein NOD- like receptor pyrin domain containing 12 (NLRP12) comes from a family of protein receptors with a wide range of functions including fertility as well as anti-inflammatory properties. The biological role of NLRP12 is poorly understood: research on the mechanisms behind its function and/or activation remains contradictory between different cell models. Current research suggests its involvement in a multi-protein complex named the inflammasome. The alternative hypothesis that has also been proposed is that NLRP12 is not a part of the inflammasome, rather it negatively regulates a transcription factor known as NF-��B down stream of Toll-like receptors. NLRP12 is …

Roles Of Gm-Csf In The Pathogenesis Of Autoimmune Diseases: An Update., Noushin Lotfi, Rodolfo Thome, Nahid Rezaei, Guang-Xian Zhang, Abbas Rezaei, A. M. Rostami, Nafiseh Esmaeil

Department of Neurology Faculty Papers

Granulocyte-macrophage colony-stimulating factor (GM-CSF) was first described as a growth factor that induces the differentiation and proliferation of myeloid progenitors in the bone marrow. GM-CSF also has an important cytokine effect in chronic inflammatory diseases by stimulating the activation and migration of myeloid cells to inflammation sites, promoting survival of target cells and stimulating the renewal of effector granulocytes and macrophages. Because of these pro-cellular effects, an imbalance in GM-CSF production/signaling may lead to harmful inflammatory conditions. In this context, GM-CSF has a pathogenic role in autoimmune diseases that are dependent on cellular immune responses such as multiple sclerosis (MS) …

Antibodies In The Diagnosis, Prognosis, And Prediction Of Psychotic Disorders., Thomas A Pollak, Jonathan P Rogers, Robert G Nagele, Mark Peakman, James M Stone, Anthony S David, Philip Mcguire

Rowan-Virtua School of Osteopathic Medicine Departmental Research

Blood-based biomarker discovery for psychotic disorders has yet to impact upon routine clinical practice. In physical disorders antibodies have established roles as diagnostic, prognostic and predictive (theranostic) biomarkers, particularly in disorders thought to have a substantial autoimmune or infective aetiology. Two approaches to antibody biomarker identification are distinguished: a "top-down" approach, in which antibodies to specific antigens are sought based on the known function of the antigen and its putative role in the disorder, and emerging "bottom-up" or "omics" approaches that are agnostic as to the significance of any one antigen, using high-throughput arrays to identify distinctive components of the …

Regulations Of Pathogenic Cd4+ T Helper Lymphocytes In Inflammatory Diseases, Handong Zheng

Biomedical Sciences ETDs

In this comprehensive project, three interrelated studies with distinct foci were employed to understand the regulations of specific CD4⁺ T helper cell population in inflammatory diseases.

Pathogenic TH17 cells play an essential role in the initiation and development of both human multiple sclerosis (MS) and animal experimental autoimmune encephalomyelitis (EAE). Nevertheless, the underlying mechanism by which the pathogenicity of TH17 cells is controlled in the autoimmune neuro-inflammation remains unclear. In aim 1, we revealed that lumican (Lum), an extracellular matrix (ECM) protein, negatively regulates encephalitic TH17 cell responses. Our findings highlighted a TH17 cell-intrinsic effect of Lum in suppressing …

Analysis Of The Local And Systemic Cytokine Response Profiles In Patients With Community-Acquired Pneumonia. Relationship With Disease Severity And Outcomes., Rafael Fernandez-Botran, Timothy Lee Wiemken, Robert R. Kelley, Paula Peyrani, Jose Bordon, Rodrigo Cavallazzi, Julio A. Ramirez

The University of Louisville Journal of Respiratory Infections

The goals of this study were to investigate the relationship of systemic and local cytokine responses with time to clinical stability (TCS) in patients with community-acquired pneumonia (CAP) and to develop a model to integrate multiple cytokine data into “cytokine response profiles” based on local vs. systemic and pro- vs. anti-inflammatory cytokine patterns in order to better understand their relationships with measures of CAP severity and outcomes. Forty hospitalized patients enrolled through the Community Acquired Pneumonia Inflammatory Study Group (CAPISG) were analyzed. Based on the ranked distribution of the levels of eight different pro-inflammatory cytokines and chemokines (IL-1b, IL-6, IL-8, …

Pneumocystis Infection Alters The Activation State Of Pulmonary Macrophages, Jessica M. Deckman, Cathryn J. Kurkjian, Joseph P. Mcgillis, Theodore J. Cory, Susan E. Birket, Linda M. Schutzman, Brian S. Murphy, Beth A. Garvy, David J. Feola

Microbiology, Immunology, and Molecular Genetics Faculty Publications

Recent studies show a substantial incidence of Pneumocystis jirovecii colonization and infection in patients with chronic inflammatory lung conditions. However, little is known about the impact of Pneumocystis upon the regulation of pulmonary immunity. We demonstrate here that Pneumocystis polarizes macrophages towards an alternatively activated macrophage-like phenotype. Genetically engineered mice that lack the ability to signal through IL-4 and IL-13 were used to show that Pneumocystis alternative macrophage activation is dependent upon signaling through these cytokines. To determine whether Pneumocystis-induced macrophage polarization would impact subsequent immune responses, we infected mice with Pneumocystis and then challenged them with Pseudomonas aeruginosa 14 …

T Cell Migration From Inflamed Skin To Draining Lymph Nodes Requires Intralymphatic Crawling Supported By Icam-1/Lfa-1 Interactions., Alvaro Teijeira, Morgan C. Hunter, Erica Russo, Steven T Proulx, Thomas Frei, Gudrun F. Debes, Marc Coles, Ignacio Melero, Michael Detmar, Ana Rouzaut, Cornelia Halin

Department of Microbiology and Immunology Faculty Papers

T cells are the most abundant cell type found in afferent lymph, but their migration through lymphatic vessels (LVs) remains poorly understood. Performing intravital microscopy in the murine skin, we imaged T cell migration through afferent LVs in vivo. T cells entered into and actively migrated within lymphatic capillaries but were passively transported in contractile collecting vessels. Intralymphatic T cell number and motility were increased during contact-hypersensitivity-induced inflammation and dependent on ICAM-1/LFA-1 interactions. In vitro, blockade of endothelial cell-expressed ICAM-1 reduced T cell adhesion, crawling, and transmigration across lymphatic endothelium and decreased T cell advancement from capillaries into lymphatic collectors …

Local Sensitivity Analysis Of Acute Inflammation, James Martin

Theses, Dissertations and Capstones

The inflammatory response is the body's response to some pathogen or foreign invader. When infected by a pathogen, a healthy individual will mount a response with immunological factors to eliminate it. An inflammatory response that is either too strong or too weak can be detrimental to the individual's health. We will look at a qualitative mathematical model of the inflammatory response, in scenarios that represent varying disorders of the immune system. Using sensitivity analysis we determine which parameters of this model are most influential in the different scenarios. By determining which parameters are most influential we can suggest possible targets …

Diffuse Traumatic Brain Injury Induces Prolonged Immune Sysregulation And Potentiates Hyperalgesia Following A Peripheral Immune Challenge, Rachel K. Rowe, Gavin I. Ellis, Jordan L. Harrison, Adam D. Bachstetter, Gregory F. Corder, Linda J. Van Eldik, Bradley K. Taylor, Francesc Marti, Jonathan Lifshitz

Microbiology, Immunology, and Molecular Genetics Faculty Publications

Background: Nociceptive and neuropathic pain occurs as part of the disease process after traumatic brain injury (TBI) in humans. Central and peripheral inflammation, a major secondary injury process initiated by the traumatic brain injury event, has been implicated in the potentiation of peripheral nociceptive pain. We hypothesized that the inflammatory response to diffuse traumatic brain injury potentiates persistent pain through prolonged immune dysregulation.

Results: To test this, adult, male C57BL/6 mice were subjected to midline fluid percussion brain injury or to sham procedure. One cohort of mice was analyzed for inflammation-related cytokine levels in cortical biopsies and serum along an …

Tuberculosis And Cardiovascular Disease: Linking The Epidemics, Moises A. Huaman, David Henson, Eduardo Ticona, Timothy R. Sterling, Beth A. Garvy

Microbiology, Immunology, and Molecular Genetics Faculty Publications

The burden of tuberculosis and cardiovascular disease (CVD) is enormous worldwide. CVD rates are rapidly increasing in low- and middle-income countries. Public health programs have been challenged with the overlapping tuberculosis and CVD epidemics. Monocyte/macrophages, lymphocytes and cytokines involved in cellular mediated immune responses against Mycobacterium tuberculosis are also main drivers of atherogenesis, suggesting a potential pathogenic role of tuberculosis in CVD via mechanisms that have been described for other pathogens that establish chronic infection and latency. Studies have shown a pro-atherogenic effect of antibody-mediated responses against mycobacterial heat shock protein-65 through cross reaction with self-antigens in human vessels. Furthermore, …

Caspase-3 Mediates The Pathogenic Effect Of Yersinia Pestis Yopm In Liver Of C57bl/6 Mice And Contributes To Yopm's Function In Spleen, Zhan Ye, Amanda A. Gorman, Annette M. Uittenbogaard, Tanya Myers-Morales, Alan M. Kaplan, Donald A. Cohen, Susan C. Straley

Microbiology, Immunology, and Molecular Genetics Faculty Publications

The virulence protein YopM of the plague bacterium Yersinia pestis has different dominant effects in liver and spleen. Previous studies focused on spleen, where YopM inhibits accumulation of inflammatory dendritic cells. In the present study we focused on liver, where PMN function may be directly undermined by YopM without changes in inflammatory cell numbers in the initial days of infection, and foci of inflammation are easily identified. Mice were infected with parent and ΔyopM-1 Y. pestis KIM5, and effects of YopM were assessed by immunohistochemistry and determinations of bacterial viable numbers in organs. The bacteria were found …

Transformation Of Human Mast Cells By Interferon-Gamma And The Potential Role Of Myeloid Derived Suppressor Cells In Mastocytosis., Sahar Lotfi-Emran

Theses and Dissertations

Mast cells respond to a variety of signals, are associated with both increased inflammation and regulation of the immune response, and are able to interact with a variety of hematopoietic and non-hematopoietic cells. The majority of the work that highlights mast cell pleiotropic abilities has been completed in murine models. Though these models have significantly advanced our understanding of what mast cells can do, they cannot inform us as to what mast cells actually do in human beings. The goal of this dissertation is to assess fully mature, primary human mast cell function beyond the well-defined type 1 hypersensitivity function …

Role Of Mir-19a Released By Inflammatory Breast Cancer Cells In The Regulation Of Dendritic Cell Functions: In Vitro Model Of Crosstalk In The Tumor Microenvironment Of Inflammatory Breast Cancer, Simone Anfossi

Dissertations and Theses (Open Access)

Inflammatory breast cancer (IBC) is a rare but very aggressive form of locally advanced breast cancer (1-6% of total breast cancer patients in United States), with a 5-year overall survival rate of only 40.5%, compared with 85% of the non-IBC patients. So far, a unique molecular signature for IBC able to explain the dramatic differences in the tumor biology between IBC and non-IBC has not been identified. As immune cells in the tumor microenvironment plays an important role in regulating tumor progression, we hypothesized that tumor-associated dendritic cells (TADC) may be responsible for regulating the development of the aggressive characteristics …