Immunology and Infectious Disease Commons^™

Plasmacytoid Dendritic Cells Sense Skin Injury And Promote Wound Healing Through Type I Interferons, Josh D. Gregorio

Dissertations & Theses (Open Access)

Plasmacytoid dendritic cells (pDCs) are a rare population of circulating cells, which selectively express intracellular Toll-like receptors (TLR)-7 and TLR-9 and have the capacity to produce large amounts of type I IFNs (IFN-a/b) in response to viruses or host derived nucleic acid containing complexes. pDCs are normally absent in skin but accumulate in the skin of psoriasis patients where their chronic activation to produce IFN-a/b drives the disease formation. Whether pDCs and their activation to produce IFN-a/b play a functional role in healthy skin is unknown. Here we show that pDCs are rapidly and transiently recruited into healthy human and …

Effects Of A Simulated Tennis Match On Lymphocyte Subset Measurements, Holly Kell

Masters Theses & Specialist Projects

Research has shown that maximal exercise has a significant effect on cells of the immune system. Specifically, lymphocyte count increases during exercise and decreases to a value lower than baseline following an acute exhaustive bout of exercise. The overall lymphocyte response is well characterized, however, the ability of exercise to affect lymphocyte subfractions is unknown to our knowledge. The purpose of this study was to assess and evaluate the affects of a simulated tennis match across two sessions on lymphocyte subsets.

Initial measurements such as age, height, weight, skinfold analysis, and heart rate were recorded for each player, as well …

Identifying Mechanisms Associated With Innate Immunity In Cows Genetically Susceptible To Mastitis, Alexandra Alida Elliott

Doctoral Dissertations

Mastitis, or mammary gland inflammation, causes the greatest loss in profit for dairy producers. Mastitis susceptibility differs among cows due to environmental, physiological, and genetic factors. Prior research identified a genetic marker in a chemokine receptor, CXCR1, associated with mastitis susceptibility and decreased neutrophil migration. Current research seeks to identify reasons behind mastitis susceptibility by validating this model through in vivo challenge with Streptococcus uberis and studying specific mechanisms causing impaired neutrophil migration. Holstein cows with GG (n=19), GC (n=28), and CC (n=20) genotypes at CXCR1+777 were challenged intramammarily with S. uberis strain UT888. After challenge 68% of quarters from …

Quantitative Trait Loci Mapping Reveals Candidate Pathways Regulating Cell Cycle Duration In Plasmodium Falciparum, Heather B. Reilly Ayala, Mark A. Wacker, Geoffrey Siwo, Michael T. Ferdig

Faculty Publications - Department of Biological & Molecular Science

Background: Elevated parasite biomass in the human red blood cells can lead to increased malaria morbidity. The genes and mechanisms regulating growth and development of Plasmodium falciparum through its erythrocytic cycle are not well understood. We previously showed that strains HB3 and Dd2 diverge in their proliferation rates, and here use quantitative trait loci mapping in 34 progeny from a cross between these parent clones along with integrative bioinformatics to identify genetic loci and candidate genes that control divergences in cell cycle duration. Results: Genetic mapping of cell cycle duration revealed a four-locus genetic model, including a major genetic effect …

The Armadillo Repeat Protein Pf16 Is Essential For Flagellar Structure And Function In Plasmodium Male Gametes, Ursula Straschil, Arthur M. Talman, David J. P. Ferguson, Karen A. Bunting, Zhengyao Xu, Elizabeth Bailes, Robert E. Sinden, Anthony A. Holder, Elizabeth F. Smith

Dartmouth Scholarship

Malaria, caused by the apicomplexan parasite Plasmodium, threatens 40% of the world's population. Transmission between vertebrate and insect hosts depends on the sexual stages of the life-cycle. The male gamete of Plasmodium parasite is the only developmental stage that possesses a flagellum. Very little is known about the identity or function of proteins in the parasite's flagellar biology. Here, we characterise a Plasmodium PF16 homologue using reverse genetics in the mouse malaria parasite Plasmodium berghei. PF16 is a conserved Armadillo-repeat protein that regulates flagellar structure and motility in organisms as diverse as green algae and mice. We show that …

Time Will Tell: Community Acceptability Of Hiv Vaccine Research Before And After The "Step Study" Vaccine Discontinuation, Paula M. Frew, Mark J. Mulligan, Su-I Hou, Kayshin Chan, Carlos Del Rio

Environmental & Occupational Health Faculty Publications

Objective This study examines whether men-who-have-sex-with-men (MSM) and transgender (TG) persons’ attitudes, beliefs, and risk perceptions toward human immunodeficiency virus (HIV) vaccine research have been altered as a result of the negative findings from a phase 2B HIV vaccine study. Design We conducted a cross-sectional survey among MSM and TG persons (N = 176) recruited from community settings in Atlanta from 2007 to 2008. The first group was recruited during an active phase 2B HIV vaccine trial in which a candidate vaccine was being evaluated (the “Step Study”), and the second group was recruited after product futility was widely reported …

Genetic Variants In Nuclear-Encoded Mitochondrial Genes Influence Aids Progression, Sher L. Hendrickson, J. A. Lautenberger, Leslie Wei Chinn, Michael Malasky, Lawrence Kingsley, James J. Goedert, Gregory D. Kirk, Edward Gomperts, Susan Buchbinder, Jennifer L. Troyer, Stephen J. O'Brien

Biology Faculty Articles

Background: The human mitochondrial genome includes only 13 coding genes while nuclear-encoded genes account for 99% of proteins responsible for mitochondrial morphology, redox regulation, and energetics. Mitochondrial pathogenesis occurs in HIV patients and genetically, mitochondrial DNA haplogroups with presumed functional differences have been associated with differential AIDS progression.

Methodology/Principal Findings: Here we explore whether single nucleotide polymorphisms (SNPs) within 904 of the estimated 1,500 genes that specify nuclear-encoded mitochondrial proteins (NEMPs) influence AIDS progression among HIV-1 infected patients. We examined NEMPs for association with the rate of AIDS progression using genotypes generated by an Affymetrix 6.0 genotyping array of 1,455 …

Distinct Macrophage Subpopulations Regulate Viral Encephalitis But Not Viral Clearance In The Cns, Christina D. Steel, Woong-Ki Kim, Larry Sanford, Laurie Wellman, Sandra Burnett, Nico Van Rooijen, Rochard P. Ciavarra

Biological Sciences Faculty Publications

Intranasal application of vesicular stomatitis virus (VSV) induces acute encephalitis characterized by a pronounced myeloid and T cell infiltrate. The role of distinct phagocytic populations on VSV encephalitis was therefore examined in this study. Ablation of peripheral macrophages did not impair VSV encephalitis or viral clearance from the brain, whereas, depletion of splenic marginal dendritic cells impaired this response and enhanced morbidity/mortality. Selective depletion of brain perivascular macrophages also suppressed this response without altering viral clearance. Thus, two anatomically distinct phagocytic populations regulate VSV encephalitis in a non-redundant fashion although neither population is essential for viral clearance in the CNS. …

Conidia But Not Yeast Cells Of The Fungal Pathogen Histoplasma Capsulatum Trigger A Type I Interferon Innate Immune Response In Murine Macrophages, Diane O. Inglis, Charlotte A. Berkes, Davina R. Hocking Murray, Anita Sil

Biology Faculty Publications

Histoplasma capsulatum is the most common cause of fungal respiratory infections and can lead to progressive disseminated infections, particularly in immunocompromised patients. Infection occurs upon inhalation of the aerosolized spores, known as conidia. Once inside the host, conidia are phagocytosed by alveolar macrophages. The conidia subsequently germinate and produce a budding yeast-like form that colonizes host macrophages and can disseminate throughout host organs and tissues. Even though conidia are the predominant infectious particle for H. capsulatum and are the first cell type encountered by the host during infection, very little is known at a molecular level about conidia or about …

Blood Kinetics Of Four Intraperitoneally Administered Therapeutic Candidate Bacteriophages In Healthy And Neutropenic Mice, Jumpei Uchiyama, Yoshihiro Maeda, Iyo Takemura, Russ Chess-Williams, Hiroshi Wakiguchi, Shigenobu Matsuzaki

Russ Chess-Williams

Due to multiple-drug resistant bacteria, phage therapy is being revisited. Although most animal experiments focus on therapeutic efficacy, the blood clearance kinetics of phages have not been well described. For further development of an efficient therapeutic strategy, information on phage blood kinetics is important. In this study, time-course concentration changes in peripheral blood of healthy and neutropenic mice were measured using four therapeutic phages (φMR11, KPP10, φEF24C, and KEP10). The results showed a two- to three-day rapid phage clearance, which fits a two-compartment model.

Blood Kinetics Of Four Intraperitoneally Administered Therapeutic Candidate Bacteriophages In Healthy And Neutropenic Mice, Jumpei Uchiyama, Yoshihiro Maeda, Iyo Takemura, Russ Chess-Williams, Hiroshi Wakiguchi, Shigenobu Matsuzaki

Russ Chess-Williams

Due to multiple-drug resistant bacteria, phage therapy is being revisited. Although most animal experiments focus on therapeutic efficacy, the blood clearance kinetics of phages have not been well described. For further development of an efficient therapeutic strategy, information on phage blood kinetics is important. In this study, time-course concentration changes in peripheral blood of healthy and neutropenic mice were measured using four therapeutic phages (φMR11, KPP10, φEF24C, and KEP10). The results showed a two- to three-day rapid phage clearance, which fits a two-compartment model.

Defining The Role Of Il-15 Trans-Presentation By Distinct Cell-Types During The Development And Homeostasis Of Natural Killer And Invariant Natural Killer T Cells, Eliseo F. Castillo

Dissertations & Theses (Open Access)

The immuno-regulatory functions displayed by NK and iNKT cells have highlighted their importance as key lymphocytes involved in innate and adaptive immunity. Therefore, understanding the dynamics influencing the generation of NK and iNKT cells is extremely important. IL-15 has been shown to provide a critical signal throughout the development and homeostasis of NK and iNKT cells; however, the cellular source of IL-15 has remained unclear. In this investigation, I provide evidence that the cell-type providing IL-15 to NK and iNKT cells via trans-presentation is determined by the tissue site and the maturation status of NK and iNKT cells. For NK …

Immune Recognition Of Self Nucleic Acids Driven By Endogenous Antimicrobial Peptides: Role In Autoimmunity, Dipyaman Ganguly

Dissertations & Theses (Open Access)

Innate immune recognition of extracellular host-derived self-DNA and self-RNA is prevented by endosomal seclusion of the Toll-like receptors (TLRs) in the dendritic cells (DCs). However, in psoriasis plasmacytoid dendritic cells have been found to be able to sense self-DNA molecules in complex with the endogenous cationic antimicrobial peptide LL37, which are internalized into the endosomal compartments and thus can access TLR9. We investigated whether this endogenous peptide can also interact with extracellular self-RNA and lead to DC activation. We found that LL37 binds self-RNA as well as self-DNA going into an electrostatic interaction; forms micro-aggregates of nano-scale particles protected from …

The Role Of Unrealistic Optimism In Explaining Preventive Behaviors In High Versus Low Endemic Malaria Settings In Belize, Daniel G. Handysides

Loma Linda University Electronic Theses, Dissertations & Projects

Background: Of all the diseases an individual can encounter in the world, malaria is one of the most destructive. Simple measures like sleeping under a bednet would greatly reduce the burden (Abeku, 2007). When people estimate their risk relative to others, they are most often unrealistically optimistic, which may explain why those at risk often fail to perform behaviors, such as using a bednet that will reduce their risk. However, one study showed that people at high risk for malaria held pessimistic perceptions of their risk for the disease, but the reasons for this finding are unclear (Morrison, Ager, & …

Characterization Of Alpha-Galactosylceramide As A Mucosal Adjuvant, Amy N. Courtney

Dissertations & Theses (Open Access)

Adjuvants are essential components of vaccine formulations that enhance adaptive immune responses to antigens, particularly for immunizations targeting the tolerogenic mucosal tissues, which are more biologically relevant for protective immunity against pathogens transmitted by the mucosal routes. Adjuvants possess the inherent capacity to bridge innate and adaptive immune responses through activating innate immune mediators. Here evidence is presented in support of the effectiveness of a synthetic glycolipid, alpha-Galactosylceramide (-GalCer), as an adjuvant for mucosal immunization with peptide and protein antigens, by oral and intranasal routes, to prime antigen-specific immune responses in multiple systemic and mucosal compartments. The adjuvant activity of …

Naive And Memory T Cell Trafficking In Selectin Ligand-Deficient Mice: The Role Of Fucosyltransferase –Iv And –Vii In The Differential Migration Of T Cell Populations, John Robert Harp

Masters Theses

The correct and timely delivery of immune cells is critical for protection against foreign antigen. In order for cells to access most organs, there are requirements that must be met to facilitate exit from the blood into extravasculature. The initial requirement is selectin-selectin ligand interactions that mediate tethering and rolling to allow shear resistance. For proper selectin-selectin ligand interaction, glycoproteins must be modified by fucosyltransferases –IV and –VII, which adds fucose to an acceptor substrate to form the sialyl-LewisX moiety. Using fucosyltransferase –IV and –VII double knockout (FtDKO) mice, we made several novel observations. Our first observation showed increased numbers …

In Memoriam: Mark Dmitrievich Sonin, 1932-2010, K. V. Galaktionov, A. J. Russ, O. Pugachev, A. Pelgunov, A. L. Kontrimavichus, Eric P. Hoberg

Harold W. Manter Laboratory of Parasitology: Faculty and Staff Publications

In memoriam for Mark Dmitrievich Sonin, parasitologist at the Russian Academy of Sciences, 1932-2010.

Interleukin-10 Mediated Autoregulation Of Murine B-1 B-Cells And Its Role In Borrelia Hermsii Infection, Vishal Sindhava, Michael E Woodman, Brian Stevenson, Subbarao Bondada

Microbiology, Immunology, and Molecular Genetics Faculty Publications

B cells are typically characterized as positive regulators of the immune response, primarily by producing antibodies. However, recent studies indicate that various subsets of B cells can perform regulatory functions mainly through IL-10 secretion. Here we discovered that peritoneal B-1 (B-1P) cells produce high levels of IL-10 upon stimulation with several Toll-like receptor (TLR) ligands. High levels of IL-10 suppressed B-1P cell proliferation and differentiation response to all TLR ligands studied in an autocrine manner in vitro and in vivo. IL-10 that accumulated in cultures inhibited B-1P cells at second and subsequent cell divisions mainly at the G1/S interphase. …

American Society Of Parasitologists Newsletter, V. 32, No. 1-2, Spring-Summer 2010, Scott Lyell Gardner

American Society of Parasitologists: Newsletter

An issue of the American Society of Parasitologists' quarterly newsletter, also called the Journal of Parasitology Newsletter.

Lps-Induced Production Of Inflammatory Mediators In The Liver Of Postnatal Animals, Valerie P. Le Rouzic

Seton Hall University Dissertations and Theses (ETDs)

Lipopolysaccharide (LPS) is the primary component of the outer membrane of Gram-negative bacteria and is responsible for the majority of inflammatory effects of infections from Gram-negative bacteria. To gain better understanding of the effects that postnatal age has on the inflammatory response, pups were randomly assigned to be treated with 250 µg/kg of LPS or saline at postnatal day (P) 1, P21, and P70. Two hours post stimulation, the pups were sacrificed and their livers were harvested for total RN A extraction. Relative mRNA levels of inflammatory genes and �-actin were determined using RT-PCR analysis with appropriate rat sense and …