Immunology and Infectious Disease Commons^™

Serpin-Derived Novel Peptide For The Treatment Against Hiv-Induced Inflammation In The Central Nervous System, Yemmy Soler

FIU Electronic Theses and Dissertations

In the brain, HIV predominantly infects microglia/macrophages and astrocytes to a lesser extent. These cells form virus reservoirs with low levels of infection that are very hard to eradicate. Even though the use of cART increases survival rate in HIV patients, the virus persists as a chronic condition. cART is not able to effectively cross the BBB, control HIV replication, or attenuate inflammation in brain reservoirs. Therefore, the virus still causes neuronal dysfunction, pain-related pathology, and ultimately HAND. In this study, we decided to test the hypothesis that a serpin-derived small peptide, SP16, can serve as an anti-viral, anti-inflammatory, pro-survival, …

Food Insecurity Is Associated With Nonalcoholic Fatty Liver Disease, Cognitive Impairment, And Immune Activation In People Living With Hiv, Javier A. Tamargo

FIU Electronic Theses and Dissertations

Food insecurity (FI) is a socioeconomic condition characterized by inadequate access to enough food and nutrition to sustain health and wellbeing. Food insecurity is a risk factor for chronic and age-related conditions, raising concerns for the aging population of people living with HIV (PLWH), in whom food insecurity is disproportionately prevalent. PLWH are at increased risk of nutrition-related complications and chronic co-morbidities, thus food insecurity may exacerbate adverse health outcomes in this population. This study investigated whether food insecurity was associated with nonalcoholic fatty liver disease (NAFLD), cognitive impairment, and immune activation among socioeconomically disadvantaged adults living with and without …

The Effect Of Age On Neurological Inflammation To Acute Sleep Fragmentation In Mice, Molly Taylor

Mahurin Honors College Capstone Experience/Thesis Projects

Obstructive sleep apnea is identified by recurring events of airway collapse during sleep, intermittent hypoxia, and perturbations in sleep continuity, known as sleep fragmentation. There is evidence to suggest that elderly patients are more at risk of developing obstructive sleep apnea. The purpose of this study was to assess whether age affects neurological inflammatory responses to acute sleep fragmentation. This assessment was made by subjecting young (4-5 months old) and old (10-11 months old) male C57BL/6j mice to automated sleep fragmentation, as well as having mice in both age categories as a control with no sleep fragmentation, for twenty-four hours. …

Interleukin-17a Facilitates Chikungunya Virus Infection By Inhibiting Ifn-Α2 Expression, Biswas Neupane, Dhiraj Acharya, Farzana Nazneen, Gabriel Gonzalez-Fernandez, Alex Sutton Flynt, Fengwei Bai

Faculty Publications

Interferons (IFNs) are the key components of innate immunity and are crucial for host defense against viral infections. Here, we report a novel role of interleukin-17A (IL-17A) in inhibiting IFN-α2 expression thus promoting chikungunya virus (CHIKV) infection. CHIKV infected IL-17A deficient (Il17a^−/−) mice expressed a higher level of IFN-α2 and developed diminished viremia and milder footpad swelling in comparison to wild-type (WT) control mice, which was also recapitulated in IL-17A receptor-deficient (Il17ra^−/−) mice. Interestingly, IL-17A selectively blocked IFN-α2 production during CHIKV, but not West Nile virus (WNV) or Zika virus (ZIKV), infections. Recombinant IL-17A …

Neutrophil-To-Lymphocyte Ratio: A Biomarker To Monitor The Immune Status Of Astronauts, Amber M. Paul, Siddhita D. Mhatre, Egle Cekanaviciute, Ann-Sofie Schreurs, Candice G.T. Tahimic, Ruth K. Globus, Sulekha Anand, Brian E. Crucian, Sharmila Bhattacharya

Publications

A comprehensive understanding of spaceflight factors involved in immune dysfunction and the evaluation of biomarkers to assess in-flight astronaut health are essential goals for NASA. An elevated neutrophil-to-lymphocyte ratio (NLR) is a potential biomarker candidate, as leukocyte differentials are altered during spaceflight. In the reduced gravity environment of space, rodents and astronauts displayed elevated NLR and granulocyte-to-lymphocyte ratios (GLR), respectively. To simulate microgravity using two well-established ground-based models, we cultured human whole blood-leukocytes in high-aspect rotating wall vessels (HARV-RWV) and used hindlimb unloaded (HU) mice. Both HARV-RWV simulation of leukocytes and HU-exposed mice showed elevated NLR profiles comparable to spaceflight …

Effects Of Alpha- And Beta-Adrenergic Receptor Blockade Upon Inflammatory Responses To Acute And Chronic Sleep Fragmentation, Nicholas David Wheeler

Masters Theses & Specialist Projects

Generally, sleep is viewed as a recuperative process and its dysregulation has

cognitive, metabolic, immunological, and inflammatory implications that are largely deleterious to human health. Epidemiological and empirical studies have suggested that sleep fragmentation (SF) as result of obstructive sleep apnea (OSA) and other sleep abnormalities leads to pronounced systemic inflammatory responses, which are influenced by the sympathetic nervous system (SNS). However, the underlying molecular mechanisms contributing to SNS regulation of SF-induced inflammatory states are not fully understood. To assess the effects of the SNS system, C57BL/6j female mice were placed in automated SF chambers (12L:12D) and subjected to either …

Defective Transcriptional Programming Of Effector Cd8 T Cells In Aged Mice Is Cell-Extrinsic And Can Be Corrected By Administration Of Il-12 And Il-18, Mladen Jergovic, Heather L. Thompson, Kristin R. Renkema, Megan J. Smithey, Janko Nikolich-Zugich

Peer Reviewed Articles

In response to infection with intracellular microorganisms, old mice mobilize decreased numbers of antigen-specific CD8 T cells with reduced expression of effector molecules and impaired cytolytic activity. Molecular mechanisms behind these defects and the cell-intrinsic (affecting naïve CD8 T cells themselves) vs. extrinsic, microenvironmental origin of such defects remain unclear. Using reciprocal transfer experiments of highly purified naïve T cells from adult and old transgenic OT-1 mice, we decisively show that the dominant effect is cell-extrinsic. Naïve adult OT-1 T cells failed to expand and terminally differentiate in the old organism infected with Listeria-OVA. This defect was preceded by …

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 Faculty Scholarship

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 …

Leukemia Inhibitory Factor Modulates The Peripheral Immune Response In A Rat Model Of Emergent Large Vessel Occlusion, Stephanie M. Davis, Lisa A. Collier, Edric D. Winford, Christopher C. Leonardo, Craig T. Ajmo Jr., Elspeth A. Foran, Timothy J. Kopper, John C. Gensel, Keith R. Pennypacker

Neurology Faculty Publications

Background: The migration of peripheral immune cells and splenocytes to the ischemic brain is one of the major causes of delayed neuroinflammation after permanent large vessel stroke. Other groups have demonstrated that leukemia inhibitory factor (LIF), a cytokine that promotes neural cell survival through upregulation of antioxidant enzymes, promotes an anti-inflammatory phenotype in several types of immune cells. The goal of this study was to determine whether LIF treatment modulates the peripheral immune response after stroke.

Methods: Young male (3 month) Sprague-Dawley rats underwent sham surgery or permanent middle cerebral artery occlusion (MCAO). Animals were administered LIF (125 μg/kg) or …

Interactions Between Aerobic Exercise Volume, Academic Stress, And Immune Function, Teresa Wiczynski

Masters Theses & Specialist Projects

Many college students exercise individually or participate in collegiate and intramural sports in addition to fulfilling their stressful academic requirements. The combination of accumulated stress and vigorous exercise could result in an impaired immune system, prompting the onset of disease and absences in class and sports practice.

Twenty-six male and female participants aged 18 to 23 were recruited for this study. Over the course of an academic semester, participants completed weekly electronic surveys documenting stress levels, aerobic exercise, and symptoms related to upper respiratory tract infections. Participants were evaluated at four different time points (Baseline, Post-Midterm Exam, Baseline Reassessment, and …

Ticks, Ixodes Scapularis, Feed Repeatedly On White-Footed Mice Despite Strong Inflammatory Response: An Expanding Paradigm For Understanding Tick-Host Interactions, Jennifer M. Anderson, Ian N. Moore, Bianca M. Nagata, José M.C. Ribeiro, Jesus G. Valenzuela, Daniel E. Sonenshine

Biological Sciences Faculty Publications

Ticks transmit infectious agents including bacteria, viruses and protozoa. However, their transmission may be compromised by host resistance to repeated tick feeding. Increasing host resistance to repeated tick bites is well known in laboratory animals, including intense inflammation at the bite sites. However, it is not known whether this also occurs in wild rodents such as white-footed mice, Peromyscus leucopus, and other wildlife, or if it occurs at all. According to the "host immune incompetence" hypothesis, if these mice do not have a strong inflammatory response, they would not reject repeated tick bites by Ixodes scapularis. To test …

Meningeal Infiltration Of The Spinal Cord By Non-Classically Activated B Cells Is Associated With Chronic Disease Course In A Spontaneous B Cell-Dependent Model Of Cns Autoimmune Disease, Amy K. Dang, Yodit Tesfagiorgis, Rajiv W. Jain, Heather C. Craig, Steven M. Kerfoot

Microbiology & Immunology Publications

We characterized B cell infiltration of the spinal cord in a B cell-dependent spontaneous model of central nervous system (CNS) autoimmunity that develops in a proportion of mice with mutant T and B cell receptors specific for myelin oligodendrocyte glycoprotein. We found that, while males are more likely to develop disease, females are more likely to have a chronic rather than monophasic disease course. B cell infiltration of the spinal cord was investigated by histology and FACs. CD4⁺ T cell infiltration was pervasive throughout the white and in some cases gray matter. B cells were almost exclusively restricted to …

Overweight/Obesity And Hiv Disease Progression In Hiv+ Adults In Botswana, Sabrina Sales Martinez

FIU Electronic Theses and Dissertations

Studies indicate that overweight and obesity protect against HIV-disease progression in antiretroviral therapy (ART)-naïve patients. We examined retrospectively the relationship of overweight/obesity with HIV-disease progression in ART-naïve HIV+ adults in Botswana in a case-control study with 18-month follow-up, which included 217 participants, 139 with BMI 18.0-24.9 kg/m² and 78 with BMI ≥25 kg/m². Archived plasma samples were used to determine inflammatory markers: leptin and bacterial endotoxin lipopolysaccharide (LPS), and genotype single nucleotide polymorphisms (SNPs) of the Fat Mass and Obesity Associated Gene (FTO).

At baseline, BMI was inversely associated with risk for AIDS-defining conditions (HR=0.218; 95%CI=0.068, 0.701, …

Gut Microbiota-Derived Short-Chain Fatty Acids, T Cells, And Inflammation, Chang Kim, Jeongho Park, Myunghoo Kim

Department of Comparative Pathobiology Faculty Publications

T cells are central players in the regulation of adaptive immunity and immune tolerance. In the periphery, T cell differentiation for maturation and effector function is regulated by a number of factors. Various factors such as antigens, co-stimulation signals, and cytokines regulate T cell differentiation into functionally specialized effector and regulatory T cells. Other factors such as nutrients, micronutrients, nuclear hormones and microbial products provide important environmental cues for T cell differentiation. A mounting body of evidence indicates that the microbial metabolites short-chain fatty acids (SCFAs) have profound effects on T cells and directly and indirectly regulate their differentiation. We …

Synergistic Effect Of Pro-Inflammatory Tnfα And Il-17 In Periostin Mediated Collagen Deposition: Potential Role In Liver Fibrosis, Suneetha Amara, Karina Lopez, Babak Banan, Sade-Kemi Brown, Margaret Whalen, Elbert L. Myles, Michael T. Ivy, Terrance Johnson, Kevin L. Schey, Venkataswarup Tiriveedhi

Biology Faculty Research

Background

The pro-inflammatory cytokines, tumor necrosis factor (TNF)-α, and interleukin (IL)-17, have been implicated in the pathogenesis of liver fibrosis. In this study, we investigated the role of TNFα and IL-17 toward induction of profibrotic factor, periostin.

Methods

HepG2 cells were cultured and treated with inflammatory cytokines, TNFα and IL-17. Computational promoter sequence analysis of the periostin promoter was performed to define the putative binding sites for transcription factors. Transcription factors were analyzed by Western blot and Chromatin Immunoprecipitation. Periostin and transcription factor expression analysis was performed by RT-PCR, Western blot, and fluorescence microscopy. Type I collagen expression from fibroblast …

Blockade Of Mast Cell Activation Reduces Cutaneous Scar Formation, Lin Chen, Megan Schrementi, Matthew J. Ranzer, Traci A. Wilgus, Luisa A. Dipietro

Faculty Publications & Research

Damage to the skin initiates a cascade of well-orchestrated events that ultimately leads to repair of the wound. The inflammatory response is key to wound healing both through preventing infection and stimulating proliferation and remodeling of the skin. Mast cells within the tissue are one of the first immune cells to respond to trauma, and upon activation they release pro-inflammatory molecules to initiate recruitment of leukocytes and promote a vascular response in the tissue. Additionally, mast cells stimulate collagen synthesis by dermal fibroblasts, suggesting they may also influence scar formation. To examine the contribution of mast cells in tissue repair, …

Serum 25-Hydroxyvitamin D Levels And C-Reactive Protein In Persons With Human Immunodeficiency Virus Infection, C. Anderson Johnson, Kalpana Poudel-Tandukar, Krishna C. Poudel, Masamine Jimba, Jun Kobayashi, Paula Palmer

CGU Faculty Publications and Research

Human immunodeficiency virus (HIV) infection has frequently been associated with vitamin D deficiency as well as chronic inflammatory response. We tested the hypothesis of an independent relationship between serum concentrations of 25-hydroxyvitamin D [25(OH)D] and high-sensitivity C-reactive protein (CRP) in a cohort of HIV-positive people. A cross-sectional survey was conducted among 316 HIV-positive people (181 men and 135 women) aged 16 to 60 years residing in the Kathmandu Valley, Nepal. Serum high-sensitivity CRP concentrations and serum 25(OH)D levels were measured by the latex agglutination nephelometry method and the competitive protein-binding assay, respectively. The relationship between serum CRP concentrations and 25(OH)D …

Neurosteroid-Mediated Regulation Of Brain Innate Immunity In Hiv/Aids: Dhea-S Suppresses Neurovirulence, Amber Paul, Ferdinand G. Maingat, Maria J. Polyak, Pornpun Vivithanaporn, Farshid Noorbakhsh, Samir Ahboucha, Glen B. Baker, Keir Pearson, Christopher Power

Publications

Neurosteroids are cholesterol-derived molecules synthesized within the brain, which exert trophic and protective actions. Infection by human and feline immunodeficiency viruses (HIV and FIV, respectively) causes neuroinflammation and neurodegeneration, leading to neurological deficits. Secretion of neuroinflammatory host and viral factors by glia and infiltrating leukocytes mediates the principal neuropathogenic mechanisms during, although the effect of neurosteroids on these processes is unknown. We investigated the interactions between neurosteroid mediated effects and lentivirus infection outcomes. Analyses of HIV-infected uninfected human brains disclosed a reduction in neurosteroid synthesis enzyme expression. Human neurons exposed to supernatants from HIV macrophages exhibited suppressed enzyme expression without …

Mechanisms Of Immunotherapeutic Intervention By Anti-Cd40l (Cd154) Antibody In An Animal Model Of Multiple Sclerosis, Laurence M. Howard, Amy J. Miga, Carol L. Vanderlugt, Mauro C. Dal Canto, John D. Laman, Randolph J. Noelle, Stephen D. Miller

Dartmouth Scholarship

Relapsing experimental autoimmune encephalomyelitis (R-EAE) in the SJL mouse is a Th1-mediated autoimmune demyelinating disease model for human multiple sclerosis and is characterized by infiltration of the central nervous system (CNS) by Th1 cells and macrophages. Disease relapses are mediated by T cells specific for endogenous myelin epitopes released during acute disease, reflecting a critical role for epitope spreading in the perpetuation of chronic central CNS pathology. We asked whether blockade of the CD40–CD154 (CD40L) costimulatory pathway could suppress relapses in mice with established R-EAE. Anti-CD154 antibody treatment at either the peak of acute disease or during remission effectively blocked …

Primary Antibody Responses To Thymus-Independent Antigens In The Lungs And Hilar Lymph Nodes Of Mice, S. Niranjan Goud, Alan M. Kaplan, Subbarao Bondada

Sanders-Brown Center on Aging Faculty Publications

B lymphocytes from the pulmonary lymphoid tissues were stimulated with a variety of thymus-independent (TI) antigens by intratracheal (i.t.) immunization. Immune responses in the lungs and hilar lymph nodes (HLN), which are part of the localized lymphoid tissue, as well as in the spleen, the systemic lymphoid organ, were studied. Thus, primary i.t. immunization of mice with the TI-1 antigen trinitrophenyl-lipopolysaccharide (TNP-LPS) elicited both antigen-specific and polyclonal plaque-forming cell responses from HLN, lung, and splenic B lymphocytes. These responses appeared as early as 3 days after immunization and declined by day 7. Similar immunization with another TI-1 antigen, TNP-Brucella …