Immunology and Infectious Disease Commons^™

Enhancement Of Reactive Oxygen Species Production And Chlamydial Infection By The Mitochondrial Nod-Like Family Member Nlrx1, Ali A. Abdul-Sater, Najwene Saïd-Sadier, Verissa M. Lam, Bhavni Singh, Matthew A. Pettengill, Fraser Soares, Ivan Tattoli, Simone Lipinski, Stephen E. Girardin, Philip Rosenstiel, David M. Ojcius

All Dugoni School of Dentistry Faculty Articles

Chlamydia trachomatis infections cause severe and irreversible damage that can lead to infertility and blindness in both males and females. Following infection of epithelial cells, Chlamydia induces production of reactive oxygen species (ROS). Unconventionally, Chlamydiae use ROS to their advantage by activating caspase-1, which contributes to chlamydial growth. NLRX1, a member of the Nod-like receptor family that translocates to the mitochondria, can augment ROS production from the mitochondria following Shigella flexneri infections. However, in general, ROS can also be produced by membrane-bound NADPH oxidases. Given the importance of ROS-induced caspase-1 activation in growth of the chlamydial vacuole, we investigated the …

Role For Sumoylation In Systemic Inflammation And Immune Homeostasis In Drosophila Larvae, Indira Paddibhatla, Mark J. Lee, Marta E. Kalamarz, Roberto Ferrarese, Shubha Govind

Publications and Research

To counter systemic risk of infection by parasitic wasps, Drosophila larvae activate humoral immunity in the fat body and mount a robust cellular response resulting in encapsulation of the wasp egg. Innate immune reactions are tightly regulated and are resolved within hours. To understand the mechanisms underlying activation and resolution of the egg encapsulation response and examine if failure of the latter develops into systemic inflammatory disease, we correlated parasitic wasp-induced changes in the Drosophila larva with systemic chronic conditions in sumoylation-deficient mutants. We have previously reported that loss of either Cactus, the Drosophila (IkB) protein or Ubc9, the SUMO-conjugating …

Campylobacter Ureolyticus: An Emerging Gastrointestinal Pathogen?, Susan Bullman, Daniel Corcoran, James O'Leary, Brigid Lucey, Deirdre Byrne, Roy D. Sleator

Department of Biological Sciences Publications

A total of 7194 faecal samples collected over a 1-year period from patients presenting with diarrhoea were screened for Campylobacter spp. using EntericBios, a multiplex-PCR system. Of 349 Campylobacter-positive samples, 23.8% were shown to be Campylobacter ureolyticus, using a combination of 16S rRNA gene analysis and highly specific primers targeting the HSP60 gene of this organism. This is, to the best of our knowledge, the first report of C. ureolyticus in the faeces of patients presenting with gastroenteritis and may suggest a role for this organism as an emerging enteric pathogen.

The Life Of An Unknown Assassin: Leon Czolgosz And The Death Of William Mckinley, Cary Federman

Department of Justice Studies Faculty Scholarship and Creative Works

The purpose of this essay is to examine the discourses that surrounded the life of Leon Czolgosz, the assassin of President William McKinley. The gaps in Czolgosz’s life, his peculiar silences, his poor health and the ambiguity and thinness of his confession, rather than taken as instances of mental and physical distress, have, instead, been understood as signs of a revolutionary anarchistic assassin. Czolgosz is an expression of a cultural tradition in somatic form. I argue that the discursive construction of criminality, already present in the late nineteenth century within the medical and human sciences, is what shaped Czolgosz’s life …

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 …

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 …

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.

A Parasitological Paradox: Why Is Ascarid Infection So Rare In The Prehistoric Americas?, Daniela Leles, Karl Reinhard, Martín Horacio Fugassa, Luis Fernando Ferreira, Alena M. Iñiguez, Adauto Araujo

Karl Reinhard Publications

Ascaris lumbricoides (giant roundworm) and Trichuris trichiura (whipworm) are the most common intestinal parasites found in humans worldwide today and they almost always co-occur. However, we find two distinct patterns in archae­ological material. In historical North American and Old World contexts, the association of A. lumbricoides and T. trich­iura is similar to the modern epidemiological picture. In contrast, the co-occurrence of A. lumbricoides and T. trichiura eggs in prehistoric South America is rare. For prehistoric contexts, T. trichiura is the most common parasite found in ar­chaeological material. Recently molecular biology techniques pointed to a subdiagnosis of roundworm infection in pre- …

Probiotic Therapy - Recruiting Old Friends To Fight New Foes, Roy D. Sleator

Department of Biological Sciences Publications

Against a backdrop of increasing antibiotic resistance, and the emergence of new and evolving pathogens, clinicians are increasingly forced to consider alternative therapies - probiotics are one such alternative.

Naïve T Cells Re-Distribute To The Lungs Of Selectin Ligand Deficient Mice, Thandi M. Onami, John R. Harp

Microbiology Publications and Other Works

BACKGROUND: Selectin mediated tethering represents one of the earliest steps in T cell extravasation into lymph nodes via high endothelial venules and is dependent on the biosynthesis of sialyl Lewis X (sLe(x)) ligands by several glycosyltransferases, including two fucosyltransferases, fucosyltransferase-IV and -VII. Selectin mediated binding also plays a key role in T cell entry to inflamed organs.

METHODOLOGY/PRINCIPAL FINDINGS: To understand how loss of selectin ligands (sLe(x)) influences T cell migration to the lung, we examined fucosyltransferase-IV and -VII double knockout (FtDKO) mice. We discovered that FtDKO mice showed significant increases (approximately 5-fold) in numbers of naïve T cells in …

Evaluating Microfossil Content Of Dental Calculus From Brazilian Sambaquis, Verônica Wesolowski, Sheila Maria Ferraz Mendonça De Souza, Karl Reinhard, Gregório Ceccantini

Karl Reinhard Publications

To date, limited numbers of dental calculus samples have been analyzed by researchers in diverse parts of the world. The combined analyses of these have provided some general guidelines for the analysis of calculus that is non-destructive to archaeological teeth. There is still a need for a quantitative study of large numbers of calculus samples to establish protocols, assess the level of contamination, evaluate the quantity of microfossils in dental calculus, and to compare analysis results with the literature concerning the biology of calculus formation. We analyzed dental calculus from 53 teeth from four Brazilian sambaquis. Sambaquis are the shellmounds …

Winter Ecology Of Buggy Creek Virus (Togaviridae, Alphavirus) In The Central Great Plains, Charles R. Brown, Stephanie A. Strickler, Amy T. Moore, Sarah A. Knutie, Abinash Padhi, Mary Bomberger Brown, Ginger R. Young, Valerie A. O'Brien, Jerome E. Foster, Nicholas Komar

School of Natural Resources: Faculty Publications

A largely unanswered question in the study of arboviruses is the extent to which virus can overwinter in adult vectors during the cold winter months and resume the transmission cycle in summer. Buggy Creek virus (BCRV; Togaviridae, Alphavirus) is an unusual arbovirus that is vectored primarily by the swallow bug (Hemiptera: Cimicidae: Oeciacus vicarius) and amplified by the ectoparasitic bug’s main avian hosts, the migratory cliff swallow (Petrochelidon pyrrhonota) and resident house sparrow (Passer domesticus). Bugs are sedentary and overwinter in the swallows’ mud nests. We evaluated the prevalence of BCRV and extent of …

Molecular Analysis Of Trypanosoma Cruzi Isolates Obtained From Raccoons (Procyon Lotor) In Warren And Barren Counties Of Kentucky, Lipeng Bi

Masters Theses & Specialist Projects

Trypanosoma cruzi, the etiologic agent of Chagas disease, infects a variety of wild mammals in the southern United States, but it has only recently been isolated from raccoons trapped in the state of Kentucky. The purpose of the present study was to use a molecular genotyping approach, followed by DNA sequencing to determine the genotypes (type I, or types IIa-IIe) of 15 of the Kentucky isolates. DNA samples were prepared from 15 T. cruzi- isolates using a Qiagen mini kit, and PCR amplification was performed using published primers for the 24S α rDNA sequence (D71 and D72), the …

Species Of Coccidia (Apicomplexa: Eimeriidae) Infecting Pikas From Alaska, U.S.A. And Northeastern Siberia, Russia, A. J. Lynch, Donald W. Duszynski, Joseph A. Cook

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

Eighty-eight fecal samples from 2 species of pika, Ochotona collaris and Ochotona hyperborea, collected in Alaska (N = 53) and Russia (N = 35), respectively, were examined for the presence of coccidia (Apicomplexa: Eimeriidae). Five oocyst morphotypes were observed. In O. collaris, we found Eimeria calentinei, Eimeria cryptobarretti, and Eimeria klondikensis, whereas in O. hyperborea, we found Eimeria banffensis, E. calentinei, E. cryptobarretti, E. klondikensis, and Isospora marquardti. This study represents new geographic records for all 5 coccidia and new host records for E. cryptobarretti and I. …

Multi-Host Model-Based Identification Of Armillifer Agkistrodontis (Pentastomida), A New Zoonotic Parasite From China, Shao-Hong Chen, Qin Liu, Yong-Nian Zhang, Jia-Xu Chen, Hao Li, Ying Chen, Peter Steinmann, Xiao-Nong Zhou

Harold W. Manter Laboratory: Library Materials

Background: Pentastomiasis is a rare parasitic infection of humans. Pentastomids are dioecious obligate parasites requiring multiple hosts to complete their life cycle. Despite their worm-like appearance, they are commonly placed into a separate sub-class of the subphylum Crustacea, phylum Arthropoda. However, their systematic position is not uncontested and historically, they have been considered as a separate phylum.

Methodology/Principal Findings: An appraisal of Armillifer agkistrodontis was performed in terms of morphology and genetic identification after its lifecycle had been established in a multi-host model, that is, mice and rats as intermediate hosts, and snakes (Agkistrodon acutus and Python molurus) …

Aspergillus Fumigatus Stimulates The Nlrp3 Inflammasome Through A Pathway Requiring Ros Production And The Syk Tyrosine Kinase, Najwane Saïd-Sadier, Eduardo V. Padilla, Gordon Langsley, David M. Ojcius

All Dugoni School of Dentistry Faculty Articles

Invasive aspergillosis (IA) is a life-threatening disease that occurs in immunodepressed patients when infected with Aspergillus fumigatus. This fungus is the second most-common causative agent of fungal disease after Candida albicans. Nevertheless, much remains to be learned about the mechanisms by which A. fulmigatus activates the innate immune system. We investigated the inflammatory response to conidia and hyphae of A. fumigatus and specifically, their capacity to trigger activation of an inflammasome. Our results show that in contrast to conidia, hyphal fragments induce NLRP3 inflammasome assembly, caspase-1 activation and IL-1β release from a human monocyte cell line. The ability of Aspergillus …

Effects Of Mold Exposure On Immune Cells, Katrin Gorham

Honors Projects in Science and Technology

The relationship between exposure to mold spores and human disease is only beginning to be understood. While evidence exists of strong correlations between moldy environments and allergic and infectious diseases, the relationship between exposure to specific species and human immune responses to them is not fully understood. This paper seeks to clarify this relationship by analyzing the effects of exposing murine immune cells to volatile organic compounds (VOCs) produced by different mold species. Mold species studied include Stachybotrys alternans; tests performed include cell viability studies and immunoassays. Results have implications for further research and treatment of mold-related diseases.

Cd1d-Dependent B-Cell Help By Nk-Like T Cells Leads To Enhanced And Sustained Production Of Bacillus Anthracis Lethal Toxin-Neutralizing Antibodies, T. Scott Devera, Lindsay M. Aye, Gillian A. Lang, Sunil K. Joshi, Jimmy D. Ballard, Mark L. Lang

Bioelectrics Publications

The current Bacillus anthracis vaccine consists largely of protective antigen (PA), the protein of anthrax toxin that mediates entry of edema factor (EF) or lethal factor (LF) into cells. PA induces protective antibody (Ab)-mediated immunity against Bacillus anthracis but has limited efficacy and duration. We previously demonstrated that activation of CD1d-restricted natural killer-like T cells (NKT) with a CD1d-binding glycolipid led to enhanced Ab titers specific for foreign antigen (Ag). We therefore tested the hypothesis that activation of NKT cells with the CD1d ligand (alpha-galactosylceramide [alpha-GC]) at the time of immunization improves PA-specific Ab responses. We observed that alpha-GC enhanced …

Identity Of Diphyllobothrium Spp. (Cestoda: Diphyllobothriidae) From Sea Lions And People Along The Pacific Coast Of South America, Robert L. Rausch, Ann M. Adams, Leo Margolis

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

Host specificity evidently is not expressed by various species of Diphyllobothrium that occur typically in marine mammals, and people become infected occasionally when dietary customs favor ingestion of plerocercoids. This report mainly concerns two species, Diphyllobothrium pacificum and Diphyllobothrium arctocephalinum, for which sea lions (Otariidae) are final hosts. The taxonomic status of those cestodes has not been clearly discernible because of misinterpretation of relationships; complex synonymies have resulted from misidentification(s). Stiles and Hassall in 1899 obtained, but did not describe, cestodes from the northern fur seal (Otariidae; Pribilof Islands). That taxon was subsequently studied by several investigators, with diverse …

Synlophe Structure In Pseudomarshallagia Elongata (Nematoda: Trichostrongyloidea) Abomasal Parasites Among Ethiopian Ungulates, With Consideration Of Other Morphological Attributes And Differentiation Within The Ostertagiinae, Eric P. Hoberg, Bersissa Kumsa, Patricia A. Pillit, Arthur Abrams

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

The independence of Pseudomarshallagia and its placement among the medium stomach worms of ungulates, Ostertagiinae, is confirmed based on comparative morphological studies of the synlophe and genital attributes among male and female specimens. An emended description of Pseudomarshallagia elongata is presented based on a series of specimens in sheep from northern Ethiopia. Pseudomarshallagia elongata is retained among the 15 genera of the Ostertagiinae based on presence of a prominent esophageal-intestinal valve, paired "0" papillae, a modified accessory bursal membrane containing the paired "7" papillae, and configuration of the copulatory bursa. The structure of the synlophe in males and females is …

Role Of All Of The Prrsv Glycoproteins In Protective Immune Response, Asit K. Pattnaik

School of Veterinary and Biomedical Sciences: Faculty Publications

Porcine reproductive and respiratory syndrome virus (PRRSV) contains the major glycoprotein, GP5, as well as three other minor glycoproteins, namely, GP2a, GP3, and GP4, on the virion envelope, all of which are required for generation of infectious virions. To study their interactions amongst each other and with the cellular receptor for PRRSV, we have cloned each of the viral glycoproteins and CD163 receptor in expression vectors and examined their expression and interaction with each other in transfected cells by co-immunoprecipitation (co-IP) assay using monospecific antibodies. Our results show that strong interaction exists between GP4 and GP5 proteins, although weak interactions …

Cell-Type Specific Distribution Of Chloride Transporters In The Rat Suprachiasmatic Nucleus, Michael A. Belenky, Patricia J. Sollars, David B. Mount, Seth L. Alper, Yosef Yarom, Gary E. Pickard

School of Veterinary and Biomedical Sciences: Faculty Publications

The suprachiasmatic nucleus (SCN) is a circadian oscillator and biological clock. Cell-to-cell communication is important for synchronization among SCN neuronal oscillators and the great majority of SCN neurons use γ-aminobutyric acid (GABA) as a neurotransmitter, the principal inhibitory neurotransmitter in the adult central nervous system. Acting via the ionotropic GABAA receptor, a chloride ion channel, GABA typically evokes inhibitory responses in neurons via Cl− influx. Within the SCN GABA evokes both inhibitory and excitatory responses although the mechanism underlying GABA-evoked excitation in the SCN is unknown. GABA-evoked depolarization in immature neurons in several regions of the brain is a function …

Porcine Reproductive And Respiratory Syndrome Virus Nonstructural Protein 1Β Modulates Host Innate Immune Response By Antagonizing Irf3 Activation, Lalit Beura, Saumendra Sarkar, Byungjoon Kwon, Sakthivel Subramaniam, Clinton J. Jones, Asit K. Pattnaik, Fernando A. Osorio

School of Veterinary and Biomedical Sciences: Faculty Publications

Porcine reproductive and respiratory syndrome virus (PRRSV) infection of swine leads to a serious disease characterized by a delayed and defective adaptive immune response. It is hypothesized that a suboptimal innate immune response is responsible for the disease pathogenesis. In the study presented here we tested this hypothesis and identified several nonstructural proteins (NSPs) with innate immune evasion properties encoded by the PRRS viral genome. Four of the total ten PRRSV NSPs tested were found to have strong to moderate inhibitory effects on beta interferon (IFN-β) promoter activation. The strongest inhibitory effect was exhibited by NSP1 followed by, NSP2, NSP11, …