DOCSLIB.ORG

The Selection of a Hepatocyte Cell Line Susceptible to Plasmodium Falciparum Sporozoite Invasion That Is Associated with Expression of Glypican-3

Total Page：16

File Type：pdf, Size：1020Kb

Download full-text PDF Read full-text
The Selection of a Hepatocyte Cell Line Susceptible to Plasmodium Falciparum Sporozoite Invasion That Is Associated with Expression of Glypican-3 fmicb-10-00127 February 27, 2019 Time: 13:2 # 1 ORIGINAL RESEARCH published: 28 February 2019 doi: 10.3389/fmicb.2019.00127 The Selection of a Hepatocyte Cell Line Susceptible to Plasmodium falciparum Sporozoite Invasion That Is Associated With Expression of Glypican-3 Rebecca E. Tweedell1,2, Dingyin Tao2†, Timothy Hamerly1,2†, Tanisha M. Robinson3†, Simon Larsen4, Alexander G. B. Grønning4, Alessandra M. Norris1, Jonas G. King2,5, Henry Chun Hin Law1, Jan Baumbach4,6‡, Elke S. Bergmann-Leitner3‡ and Rhoel R. Dinglasan1,2* 1 Department of Infectious Diseases and Immunology, Emerging Pathogens Institute, University of Florida, Gainesville, FL, Edited by: United States, 2 W. Harry Feinstone Department of Molecular Microbiology and Immunology, Johns Hopkins Malaria Celio Geraldo Freire-de-Lima, Research Institute, Johns Hopkins Bloomberg School of Public Health, Baltimore, MD, United States, 3 Malaria Vaccine Universidade Federal do Rio Branch, Walter Reed Army Institute of Research, Silver Spring, MD, United States, 4 Computational BioMedicine Lab, de Janeiro, Brazil Department of Mathematics and Computer Science, University of Southern Denmark, Odense, Denmark, 5 Department Reviewed by: of Biochemistry, Molecular Biology, Entomology & Plant Pathology, Mississippi State University, Starkville, MS, United States, Rodrigo Andrés López-Muñoz, 6 Chair of Experimental Bioinformatics, TUM School of Life Sciences Weihenstephan, Technical University of Munich, Southern University of Chile, Chile Munich, Germany Miguel Prudêncio, University of Lisbon, Portugal In vitro studies of liver stage (LS) development of the human malaria parasite *Correspondence: Rhoel R. Dinglasan Plasmodium falciparum are technically challenging; therefore, fundamental questions [email protected]fl.edu about hepatocyte receptors for invasion that can be targeted to prevent infection remain †These authors have contributed unanswered. To identify novel receptors and to further understand human hepatocyte equally to this work ‡These authors also contributed susceptibility to P. falciparum sporozoite invasion, we created an optimized in vitro equally to this work system by mimicking in vivo liver conditions and using the subcloned HC-04.J7 cell line that supports mean infection rates of 3–5% and early development of P. falciparum Specialty section: This article was submitted to exoerythrocytic forms—a 3- to 5-fold improvement on current in vitro hepatocarcinoma Infectious Diseases, models for P. falciparum invasion. We juxtaposed this invasion-susceptible cell line a section of the journal with an invasion-resistant cell line (HepG2) and performed comparative proteomics Frontiers in Microbiology and RNA-seq analyses to identify host cell surface molecules and pathways important Received: 13 October 2018 Accepted: 21 January 2019 for sporozoite invasion of host cells. We identified and investigated a hepatocyte cell Published: 28 February 2019 surface heparan sulfate proteoglycan, glypican-3, as a putative mediator of sporozoite Citation: invasion. We also noted the involvement of pathways that implicate the importance Tweedell RE, Tao D, Hamerly T, Robinson TM, Larsen S, of the metabolic state of the hepatocyte in supporting LS development. Our study Grønning AGB, Norris AM, King JG, highlights important features of hepatocyte biology, and specifically the potential role of Law HCH, Baumbach J, glypican-3, in mediating P. falciparum sporozoite invasion. Additionally, it establishes a Bergmann-Leitner ES and Dinglasan RR (2019) The Selection simple in vitro system to study the LS with improved invasion efficiency. This work paves of a Hepatocyte Cell Line Susceptible the way for the greater malaria and liver biology communities to explore fundamental to Plasmodium falciparum Sporozoite Invasion That Is Associated With questions of hepatocyte-pathogen interactions and extend the system to other human Expression of Glypican-3. malaria parasite species, like P. vivax. Front. Microbiol. 10:127. doi: 10.3389/fmicb.2019.00127 Keywords: malaria, Plasmodium falciparum, liver stage, in vitro model, omics, glypican-3, hepatocyte Frontiers in Microbiology| www.frontiersin.org 1 February 2019| Volume 10| Article 127 fmicb-10-00127 February 27, 2019 Time: 13:2 # 2 Tweedell et al. Hepatocyte Susceptibility to P. falciparum Invasion INTRODUCTION can be distributed as a shared resource to laboratories all over the world. Malaria is a devastating disease that affects over 200 million Technical limitations of studying the mammalian Plasmodium people each year and causes approximately 445,000 deaths, LS have hampered the identification of proteins involved mainly among young children (WHO, 2017). Plasmodium in sporozoite host cell invasion and infection and left the falciparum is one of the major parasites responsible for morbidity process poorly understood for P. falciparum. Most studies and mortality. This parasite is transmitted to humans as a have focused on the rodent Plasmodium species. However, sporozoite through the bite of an infected female anopheline differences in sporozoite host cell tropism and the lack mosquito during blood feeding. From the bite site, the sporozoite of conservation of hepatocyte surface receptors necessary makes its way to the liver, where it infects a hepatocyte for invasion suggest significant differences exist between (Yamauchi et al., 2007). The infection of hepatocytes causes these species and P. falciparum (Kaushansky and Kappe, no clinical symptoms, allowing the parasite to develop and 2015); focusing studies on rodent parasites alone can cause multiply to prepare for the invasion of red blood cells, which essential factors for P. falciparum sporozoite invasion to be results in clinical disease (Phillips and Pasvol, 1992; Vaughan missed or overlooked. Using various model systems, it has et al., 2008). The LS is a crucial step in the parasite’s life been demonstrated that SCARB1 (Rodrigues et al., 2008), cycle, as it establishes vertebrate infection; however, studying SDC2 (Frevert et al., 1993), EphA2 (Kaushansky et al., P. falciparum LS development has been technically challenging. 2015), LRP1 (Shakibaei and Frevert, 1996), CD81 (Silvie Studies carried out using primary human hepatocytes face the et al., 2003), and c-Met (P. berghei only; Kaushansky and obstacles of these cells not propagating in culture, being in Kappe, 2011) can each play a role as hepatocyte receptors short supply, and producing highly variable infection rates (0.13– for sporozoite invasion and infection, but the molecular 2%) (Smith et al., 1984; Mazier et al., 1985; Vaughan et al., invasion mechanism for P. falciparum remains largely unknown. 2008; Roth et al., 2018). While recent work has improved the Additionally, the steps of LS development following sporozoite utility of primary cells, this system requires the screening of invasion are not well defined for P. falciparum. These different lots of primary cells to identify those that support knowledge gaps in LS biology, along with the difficulty of sporozoite invasion and development, limiting widespread use implementing high-throughput screens for this stage, have (Roth et al., 2018). Development of a suitable alternative to using been major roadblocks in identifying much needed drug primary human hepatocytes for the study of the P. falciparum targets and vaccine candidates (Derbyshire et al., 2012; LS is desirable. Longley et al., 2015). P. falciparum and P. vivax sporozoites can infect and develop Herein, we applied comparative proteomics and RNA- in the human hepatocarcinoma cell line HC-04, but infection seq approaches to identify surface molecules and pathways efficiency remains marginal, customarily between 0.13% and 0.7– from P. falciparum sporozoite invasion-susceptible and 1% for P. falciparum (Sattabongkot et al., 2006; Mikolajczak et al., invasion-resistant hepatocarcinoma cell lines that are 2011; Tao et al., 2014). HC-04 is a spontaneously immortalized potentially important for P. falciparum sporozoite invasion. cell line that was isolated from normal human hepatocytes We further investigated GPC3 as a putative receptor mediating (Prachumsri and Yimamnuaychok, 2002). Recent analyses of this sporozoite invasion of hepatocytes using a robust platform for line suggest that, unlike other commonly used hepatocarcinoma P. falciparum sporozoite invasion of and early exoerythrocytic cell lines, like HepG2, HC-04 exhibits more plasticity and a form development in a hepatocarcinoma line. This platform greater propensity to recover its epithelial characteristics (Tao effectively overcomes the cost barrier and high variability of et al., 2014), opening the possibility to create a sporozoite primary human tissue and expands the utility of in vitro culture invasion system based on this line. Such a system would greatly for LS studies. The comparative multi-omics dataset identifies improve the ability to perform high-throughput drug screening other important host cell pathways that may also influence for LS compounds (malERA Refresh Consultative Panel on hepatocyte susceptibility to P. falciparum sporozoite invasion, Basic Science and Enabling Technology, 2017) and study the spurring hypothesis generation and testing by the greater biology of the LS in a homogeneous population of cells that scientific community. Abbreviations: ACN, acetonitrile; ALPK2, alpha kinase 2; BSA, bovine serum MATERIALS AND METHODS albumin; CLDN1, claudin; CM, culture media; CSP, circumsporozoite protein; DCBLD2, discoidin, CUB, and LCCL domain containing protein
Load more

Recommended publications
  • Research Toward Vaccines Against Malaria
    © 1998 Nature Publishing Group http://www.nature.com/naturemedicine REVIEW Louis Miller (National Institute of Allergy and Infectious Diseases) and Stephen Hoffman (Naval Medical Research Institute) review progress toward developing malaria vaccines. They argue that multiple antigens from different stages may be needed to protect the diverse populations at risk, and that an optimal vaccine would Induce Immunity against all stages. Vaccines for African children, In whom the major mortality occurs, must induce immunity against ase,cual blood stages. Research toward vaccines against malaria Malaria is one of the major causes of the only stage of the life cycle that causes disease and death between the Tropic LOUIS H. MILLER1 disease. The stages before the asexual of Cancer and Tropic of Capricorn. & STEPHEN L. HOFFMAN2 blood stage are lumped together and Plasmodium falciparum has an especially called pre-erythrocytic. A small propor­ profound impact on infants and children in sub-Saharan Africa, tion of the asexual blood stages differentiate into sexual stages, where its effect on health is increasing as chloroquine resistance the gametocytes in red cells that infect mosquitoes; vaccines to spreads across the continent. We believe that vaccination the mosquito stages are called transmission-blocking vaccines. against P. falciparum is the intervention with the greatest poten­ The parasites' multistage life cycle and the fact that immune re­ tial to reduce malaria-associated severe morbidity and mortality sponses that recognize one stage often do not affect the next in areas with the most intense transmission and that it may do stage have made vaccine development for malaria more diffi­ so without necessarily preventing blood stage infection.
    [Show full text]
  • Unexpected Fold in the Circumsporozoite Protein Target of Malaria Vaccines
    Unexpected fold in the circumsporozoite protein target of malaria vaccines Michael B. Doud, Adem C. Koksal, Li-Zhi Mi, Gaojie Song, Chafen Lu, and Timothy A. Springer1 Immune Disease Institute, Children’s Hospital Boston and Department of Biological Chemistry and Molecular Pharmacology, Harvard Medical School, Boston, MA 02115 Contributed by Timothy A. Springer, April 4, 2012 (sent for review March 19, 2012) Circumsporozoite (CS) protein is the major surface component of Plas- The CS structures reveal a unique “αTSR” domain that is modium falciparum sporozoites and is essential for host cell invasion. related to TSR domains yet has unique features (Figs. 1 C and D A vaccine containing tandem repeats, region III, and thrombospondin and 2). Region III forms an integral part of the fold as a unique type-I repeat (TSR) of CS is efficacious in phase III trials but gives only amphipathic α-helix running orthogonally to the classic three- a 35% reduction in severe malaria in the first year postimmunization. stranded TSR homology region. This α1-helix, together with We solved crystal structures showing that region III and TSR fold into a “CS flap” (Fig. 1 C and D), decorates one face of the TSR asingleunit,an“αTSR” domain. The αTSR domain possesses a hydro- β-sheet (Fig. 2A). By packing against the β-sheet, the region III phobic pocket and core, missing in TSR domains. CS binds heparin, but α-helix gives the αTSR domain a hydrophobic core lacking in αTSR does not. Interestingly, polymorphic T-cell epitopes map to spe- TSR domains. A short linker containing a conserved hydro- cialized αTSR regions.
    [Show full text]
  • Professor Salimata Thurston Née Wade
    2010 Winner of AU-ECOWAS Women Scientists Award Life Sciences and Earth Professor Salimata Thurston née Wade Mrs. Salimata Thurston née Wade is a top-notch tenured Professor of Physiology and Human Nutrition at the Faculty of Sciences and Technology of Université Cheikh Anta Diop, Dakar (UCAD). She was Head of Department of Animal Biology of the FST, UCAD from 2004 to 2006 and currently serves as Director of the Nutrition Laboratory and is in charge of doctoral training at the Ecole Doctorale ED-SEV of UCAD. Born in Dakar, at the Médina, on 28 February 1951, Mrs. Wade completed her primary education in Dakar and continued with secondary education at the Lycée Carnot School for Young Girls later known as Lycée John F. Kennedy. She obtained her baccalauréat D with honours in 1972. She continued her education in France at the Université Paris 7 and specialized in Physiology and General Human Biology, with focus on Nutrition. In 1978, she joined INSERM’s prestigious Unit 1 for Research in Nutrition of the Bichat Hospital. Mrs Wade would spend 9 years there in order to carry out research, particularly on biological signs of malnutrition and effects of interplay between malnutrition and infection. In 1986, Mrs Wade defended her Doctoral thesis on the theme “Transthyretin (Prealbumine) and Thymuline (Zn-FTS) in Protein- Energy Malnutrition” at the Université Paris 7. She was awarded High Honours by the jury. She also underwent several internships in various laboratories, such as Dunn Nutrition Laboratory of the Medical Research Council (HNR) o f Cambridge, England in order to specialise in the measurement of energy expenditure in men and the use of stable isotopes in nutrition.
    [Show full text]
  • Based on the Circumsporozoite Protein Protein: a Case Study With
    Adjuvant-like Effect of Vaccinia Virus 14K Protein: A Case Study with Malaria Vaccine Based on the Circumsporozoite Protein This information is current as Aneesh Vijayan, Carmen E. Gómez, Diego A. Espinosa, of September 26, 2021. Alan G. Goodman, Lucas Sanchez-Sampedro, Carlos Oscar S. Sorzano, Fidel Zavala and Mariano Esteban J Immunol published online 21 May 2012 http://www.jimmunol.org/content/early/2012/05/21/jimmun ol.1102492 Downloaded from Supplementary http://www.jimmunol.org/content/suppl/2012/05/21/jimmunol.110249 Material 2.DC1 http://www.jimmunol.org/ Why The JI? Submit online. • Rapid Reviews! 30 days* from submission to initial decision • No Triage! Every submission reviewed by practicing scientists • Fast Publication! 4 weeks from acceptance to publication by guest on September 26, 2021 *average Subscription Information about subscribing to The Journal of Immunology is online at: http://jimmunol.org/subscription Permissions Submit copyright permission requests at: http://www.aai.org/About/Publications/JI/copyright.html Email Alerts Receive free email-alerts when new articles cite this article. Sign up at: http://jimmunol.org/alerts The Journal of Immunology is published twice each month by The American Association of Immunologists, Inc., 1451 Rockville Pike, Suite 650, Rockville, MD 20852 Copyright © 2012 by The American Association of Immunologists, Inc. All rights reserved. Print ISSN: 0022-1767 Online ISSN: 1550-6606. Published May 21, 2012, doi:10.4049/jimmunol.1102492 The Journal of Immunology Adjuvant-like Effect of Vaccinia Virus 14K Protein: A Case Study with Malaria Vaccine Based on the Circumsporozoite Protein Aneesh Vijayan,* Carmen E. Go´mez,* Diego A.
    [Show full text]
  • Presence of a Circumsporozoite-Like Protein in Micronemes of Blood-Stage Merozoites of Malaria Parasites A.H
    Presence of a circumsporozoite-like protein in micronemes of blood-stage merozoites of malaria parasites A.H. Cochrane,1 S. Uni,2 M. Maracic,' L. di Giovanni,1 M. Aikawa,2 & R.S. Nussenzweig1 We demonstrate for the first time the presence of a circumsporozoite (CS)-like protein in invasive blood stages of malaria parasites. Immunogold electron microscopy using antisporozoite monoclonal antibodies localized these antigens in the micronemes of merozoites. Western immunoblot and two-dimensional gel electrophoresis of mature blood-stage extracts of Plasmodium falciparum, P. berghei, P. cynomolgi, and P. brasilianum identified polypeptides having the same apparent molecular mass and isoelectric points as the corresponding sporozoite (CS) proteins. The CS-like protein of merozoites is present in relatively minor amounts, compared to the CS protein of sporozoites. Mice with long-term P. berghei blood-induced infections develop antibodies which react with sporozoites. Introduction cursors have been demonstrated in the micronemes of Sporozoites are the invasive stage of plasmodia in- sporozoites (7). oculated into the vertebrate host by the bite of An- opheles mosquitos. Their surface membrane is covered Methods and results by the circumsporozoite (CS) protein which arises CS proteins, like the protective response they induce, from higher M, (relative molecular mass) precursors. have been considered to be stage specific (reviewed in All CS proteins contain an immunodominant region 1). In the present study, using antisporozoite mAbs we consisting of a single epitope which is tandemly re- have demonstrated, for the first time, the presence of peated and species specific. Monoclonal antibodies CS-like proteins in the micronemes of blood-stage (mAbs) directed against this repeat region inhibit merozoites of P.
    [Show full text]
  • A T-Cell Response to a Liver-Stage Plasmodium Antigen Is Not Boosted by Repeated Sporozoite Immunizations
    A T-cell response to a liver-stage Plasmodium antigen is not boosted by repeated sporozoite immunizations Sean C. Murphya, Arnold Kasb, Brad C. Stoneb, and Michael J. Bevanc,d,1 aDepartment of Laboratory Medicine, University of Washington Medical Center, Seattle, WA 98195; bBenaroya Research Institute, Seattle, WA 98101; and cDepartment of Immunology, and dThe Howard Hughes Medical Institute, University of Washington, Seattle, WA 98195 Contributed by Michael J. Bevan, March 1, 2013 (sent for review February 2, 2013) + Development of an antimalarial subunit vaccine inducing protective instead associated with antibodies and CD4 T-cell responses (21). cytotoxic T lymphocyte (CTL)-mediated immunity could pave the way Thus, CSP is an important but currently insufficient target for use for malaria eradication. Experimental immunization with sporozoites as a single-antigen vaccine. Because responses to non-CSP anti- induces this type of protective response, but the extremely large gens can protect in the absence of CSP-specific immunity in mice number of proteins expressed by Plasmodium parasites has so far (11, 22–25), we and others are working to discover novel protective prohibited the identification of sufficient discrete T-cell antigens to antigens to broaden the immune repertoire. develop subunit vaccines that produce sterile immunity. Here, using Single immunization using CPS or late-arresting GAP ap- mice singly immunized with Plasmodium yoelii sporozoites and high- proaches usually provides greater protection than an equivalent throughput screening, we identified a unique CTL response against number of RAS parasites (11, 26). RAS parasites arrest shortly after the parasite ribosomal L3 protein. Unlike CTL responses to the circum- hepatocyte infection, whereas GAPs progress further depending on sporozoite protein (CSP), the population of L3-specific CTLs was not the specific genetic lesion.
    [Show full text]
  • Apicomplexan Cytoskeleton and Motors: Key Regulators in Morphogenesis, Cell Division, Transport and Motility
    International Journal for Parasitology 39 (2009) 153–162 Contents lists available at ScienceDirect International Journal for Parasitology journal homepage: www.elsevier.com/locate/ijpara Invited Review Apicomplexan cytoskeleton and motors: Key regulators in morphogenesis, cell division, transport and motility Joana M. Santos a, Maryse Lebrun b, Wassim Daher a, Dominique Soldati a, Jean-Francois Dubremetz b,* a Department of Microbiology and Molecular Medicine, Faculty of Medicine–University of Geneva CMU, 1 rue Michel-Servet, 1211 Geneva 4, Switzerland b UMR CNRS 5235, Bt 24, CC 107 Université de Montpellier 2, Place Eugène Bataillon, 34095 Montpellier cedex 05, France article info abstract Article history: Protozoan parasites of the phylum Apicomplexa undergo a lytic cycle whereby a single zoite produced by Received 30 July 2008 the previous cycle has to encounter a host cell, invade it, multiply to differentiate into a new zoite gen- Received in revised form 13 October 2008 eration and escape to resume a new cycle. At every step of this lytic cycle, the cytoskeleton and/or the Accepted 16 October 2008 gliding motility apparatus play a crucial role and recent results have elucidated aspects of these pro- cesses, especially in terms of the molecular characterization and interaction of the increasing number of partners involved, and the signalling mechanisms implicated. The present review aims to summarize Keywords: the most recent findings in the field. Apicomplexa Ó 2008 Australian Society for Parasitology Inc. Published by Elsevier Ltd.
    [Show full text]
  • Role of Opsonophagocytosis in Immune Protection Against Malaria
    Review Role of Opsonophagocytosis in Immune Protection against Malaria Wolfgang W. Leitner 1, Megan Haraway 2, Tony Pierson 2 and Elke S. Bergmann-Leitner 2,* 1 Basic Immunology Branch, Division of Allergy, Immunology, and Transplantation/National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD 20852, USA; [email protected] 2 Immunology Core/Malaria Biologics Branch, Walter Reed Army Institute of Research, Silver Spring, MD 20910, USA; [email protected] (M.H.); [email protected] (T.P.) * Correspondence: [email protected]; Tel.: +1-301-319-9278 Received: 8 May 2020; Accepted: 26 May 2020; Published: 30 May 2020 Abstract: The quest for immune correlates of protection continues to slow vaccine development. Todate, only vaccine-induced antibodies have been confirmed as direct immune correlates of protection against a plethora of pathogens. Vaccine immunologists, however, have learned through extensive characterizations of humoral responses that the quantitative assessment of antibody responses alone often fails to correlate with protective immunity or vaccine efficacy. Despite these limitations, the simple measurement of post-vaccination antibody titers remains the most widely used approaches for vaccine evaluation. Developing and performing functional assays to assess the biological activity of pathogen-specific responses continues to gain momentum; integrating serological assessments with functional data will ultimately result in the identification of mechanisms that contribute to protective immunity and will guide vaccine development. One of these functional readouts is phagocytosis of antigenic material tagged by immune molecules such as antibodies and/or complement components. This review summarizes our current understanding of how phagocytosis contributes to immune defense against pathogens, the pathways involved, and defense mechanisms that pathogens have evolved to deal with the threat of phagocytic removal and destruction of pathogens.
    [Show full text]
  • Malaria Liver Stage Parasites Strategies for Immune Evasion and Host Modulation: Implication for Vaccine Design
    Open Access Austin Journal of Vaccines & Immunotherapeutics Mini Review Malaria Liver Stage Parasites Strategies for Immune Evasion and Host Modulation: Implication for Vaccine Design Dabbu Kumar Jaijyan1, Himanshu Singh1 and Agam Prasad Singh1* Abstract Infectious Diseases Laboratory, National Institute of Malaria is a devastating infectious disease caused by protozoan parasite Immunology, India of the genus Plasmodium. When an infected mosquito bites a vertebrate host *Corresponding author: Singh AP, National Institute it leaves a small number of sporozoites under the skin. Sporozoites from the of Immunology, Aruna Asaf Ali Marg, New Delhi-110067, site of bite, end up in lymph node or liver. In the lymph node these parasite India. Tel: (+91-11) 26703707; 26715032; Fax: +91-11- are degraded and act as source of antigen for the immune system. In liver, the 26717104; Email: [email protected] sporozoites invade into a hepatocyte and develop into mature schizonts. Liver stage parasites are able to evade host immune responses as well as modulate Received: July 19, 2014; Accepted: September 30, the various host pathways. Study of Plasmodium liver stage exportome may 2014; Published: October 16, 2014 provide valuable vaccine candidates and those with strong T cell epitope may be inducted into pre erythrocytic stage vaccine pipeline. Hepatocytes process and present foreign antigens on its surface hence some of the Plasmodium exported proteins are also likely presented on its surface similar to circumsporozoite protein. In terms of designing vaccine delivery system and the antigen load in liver, recent advances suggest that one need to deliver antigen in <20% of hepatocytes. Presence of antigen in large population of hepatocytes (>25%) leads to silencing of CTLs, which are no longer effective in killing the pathogens.
    [Show full text]
  • Evaluating Seroprevalence to Circumsporozoite Protein to Estimate Exposure to Three Species of Plasmodium in the Brazilian Amazo
    Pereira et al. Infectious Diseases of Poverty (2018) 7:46 https://doi.org/10.1186/s40249-018-0428-1 RESEARCH ARTICLE Open Access Evaluating seroprevalence to circumsporozoite protein to estimate exposure to three species of Plasmodium in the Brazilian Amazon Virginia Araujo Pereira1, Juan Camilo Sánchez-Arcila1, Mariana Pinheiro Alves Vasconcelos2, Amanda Ribeiro Ferreira1, Lorene de Souza Videira1, Antonio Teva3, Daiana Perce-da-Silva4, Maria Teresa Queiroz Marques5, Luzia Helena de Carvalho6, Dalma Maria Banic4, Luiz Cristóvão Sobrino Pôrto5 and Joseli Oliveira-Ferreira1* Abstract Background: Brazil has seen a great decline in malaria and the country is moving towards elimination. However, for eventual elimination, the control program needs efficient tools in order to monitor malaria exposure and transmission. In this study, we aimed to evaluate whether seroprevalence to the circumsporozoite protein (CSP) is a good tool for monitoring the exposure to and/or evaluating the burden and distribution of Plasmodium species in the Brazilian Amazon. Methods: Cross-sectional surveys were conducted in a rural area of Porto Velho, Rondônia state. Parasite infection was detected by microscopy and polymerase chain reaction. Antibodies to the sporozoite CSP repeats of Plasmodium vivax, P. falciparum,andP. malariae (PvCS, PfCS, and PmCS) were detected using the enzyme-linked immunosorbent assay technique. Human leukocyte antigen (HLA)-DRB1 and DQB1 genes were typed using Luminex® xMAP® technology. Results: The prevalence of immunoglobulin G against P. vivax CSP peptide (62%) was higher than P. falciparum (49%) and P. malariae (46%) CSP peptide. Most of the studied individuals had antibodies to at least one of the three peptides (72%), 34% had antibodies to all three peptides and 28% were non-responders.
    [Show full text]
  • The Role of Rhomboid Proteases and a Oocyst Capsule Protein
    THE ROLE OF RHOMBOID PROTEASES AND A OOCYST CAPSULE PROTEIN IN MALARIA PATHOGENESIS AND PARASITE DEVELOPMENT BY PRAKASH SRINIVASAN Submitted in partial fulfillment of the requirements For the degree of Doctor of Philosophy Thesis Advisor: Prof. Marcelo Jacobs-Lorena Department of Genetics CASE WESTERN RESERVE UNIVERSITY August, 2007 CASE WESTERN RESERVE UNIVERSITY SCHOOL OF GRADUATE STUDIES We hereby approve the dissertation of ______________________________________________________ candidate for the Ph.D. degree *. (signed)_______________________________________________ (chair of the committee) ________________________________________________ ________________________________________________ ________________________________________________ ________________________________________________ ________________________________________________ (date) _______________________ *We also certify that written approval has been obtained for any proprietary material contained therein. TABLE OF CONTENTS Table of Contents 1 List of Tables 2 List of Figures 4 Acknowledgements 5 Abstract 7 CHAPTER 1: Introduction and Research Objectives 9 Introduction 10 Malaria: History and Facts 10 Discovery of Mosquitoes as vectors 10 Malaria: Life Cycle 12 Life cycle in the vertebrate host 12 Life cycle in the mosquito 15 Sporozoite invasion of the liver 29 Study of gene function in parasites 32 Research Objectives 34 CHAPTER 2: Analysis of Plasmodium and Anopheles Transcriptomes during Oocyst Differentiation 37 CHAPTER 3: PbCap380, a novel Plasmodium Oocyst Capsule Protein
    [Show full text]
  • Mechanisms of Escape from Host Immune Defenses by Apicomplexan Parasites
    Iowa State University Capstones, Theses and Creative Components Dissertations Spring 2020 Mechanisms of Escape from Host Immune Defenses by Apicomplexan Parasites Reannan Barlow Follow this and additional works at: https://lib.dr.iastate.edu/creativecomponents Part of the Parasitology Commons Recommended Citation Barlow, Reannan, "Mechanisms of Escape from Host Immune Defenses by Apicomplexan Parasites" (2020). Creative Components. 470. https://lib.dr.iastate.edu/creativecomponents/470 This Creative Component is brought to you for free and open access by the Iowa State University Capstones, Theses and Dissertations at Iowa State University Digital Repository. It has been accepted for inclusion in Creative Components by an authorized administrator of Iowa State University Digital Repository. For more information, please contact [email protected]. Mechanisms of Escape from Host Immune Defenses by Apicomplexan Parasites Review Article by Reannan Barlow Overview: A successful pathogen manipulates its host from the moment infection occurs. Apicomplexan parasites are no different. Plasmodium spp., the causative agents of malaria, evade the human immune system so well that they kill hundreds of thousands of people per year. Toxoplasma, though not particularly dangerous to a healthy adult, is a widespread pathogen due to how easily it spreads between host and how it modulates host functions (27). This review discusses how Toxoplasma and Plasmodium avoid clearance by host defenses, highlighting their similarities and differences. Background: Malaria: Malaria is an arthropod-borne disease resulting from an infection with a protozoan parasite of the genus Plasmodium belonging to the phylum Apicomplexa (14). This parasite is arguably, one of the deadliest parasites across the globe. According to the World Health Organization, there were roughly 228 million cases of malaria worldwide and 405,000 deaths in 2018 (10).
    [Show full text]