{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,29]],"date-time":"2026-09-29T20:15:29Z","timestamp":1790712929991,"version":"4.1.0"},"reference-count":105,"publisher":"eLife Sciences Publications, Ltd","license":[{"start":{"date-parts":[[2021,3,2]],"date-time":"2021-03-02T00:00:00Z","timestamp":1614643200000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"},{"start":{"date-parts":[[2021,3,2]],"date-time":"2021-03-02T00:00:00Z","timestamp":1614643200000},"content-version":"am","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"},{"start":{"date-parts":[[2021,3,2]],"date-time":"2021-03-02T00:00:00Z","timestamp":1614643200000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100000265","name":"Medical Research Council","doi-asserted-by":"publisher","award":["G40270"],"award-info":[{"award-number":["G40270"]}],"id":[{"id":"10.13039\/501100000265","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100000265","name":"Medical Research Council","doi-asserted-by":"publisher","award":["MR\/M003906\/1"],"award-info":[{"award-number":["MR\/M003906\/1"]}],"id":[{"id":"10.13039\/501100000265","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100004440","name":"Wellcome Trust","doi-asserted-by":"publisher","award":["WT206194"],"award-info":[{"award-number":["WT206194"]}],"id":[{"id":"10.13039\/100004440","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100004440","name":"Wellcome Trust","doi-asserted-by":"publisher","award":["203783\/Z\/16\/Z"],"award-info":[{"award-number":["203783\/Z\/16\/Z"]}],"id":[{"id":"10.13039\/100004440","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100004440","name":"Wellcome Trust","doi-asserted-by":"publisher","award":["104111\/Z\/14\/Z"],"award-info":[{"award-number":["104111\/Z\/14\/Z"]}],"id":[{"id":"10.13039\/100004440","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100004440","name":"Wellcome Trust","doi-asserted-by":"publisher","award":["106917\/Z\/15\/Z"],"award-info":[{"award-number":["106917\/Z\/15\/Z"]}],"id":[{"id":"10.13039\/100004440","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100004440","name":"Wellcome Trust","doi-asserted-by":"publisher","award":["WT084226"],"award-info":[{"award-number":["WT084226"]}],"id":[{"id":"10.13039\/100004440","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100004440","name":"Wellcome Trust","doi-asserted-by":"publisher","award":["107668\/Z\/15\/Z"],"award-info":[{"award-number":["107668\/Z\/15\/Z"]}],"id":[{"id":"10.13039\/100004440","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["elifesciences.org"],"crossmark-restriction":false},"short-container-title":[],"abstract":"<jats:p>Falciparum malaria is clinically heterogeneous and the relative contribution of parasite and host in shaping disease severity remains unclear. We explored the interaction between inflammation and parasite variant surface antigen (VSA) expression, asking whether this relationship underpins the variation observed in controlled human malaria infection (CHMI). We uncovered marked heterogeneity in the host response to blood challenge; some volunteers remained quiescent, others triggered interferon-stimulated inflammation and some showed transcriptional evidence of myeloid cell suppression. Significantly, only inflammatory volunteers experienced hallmark symptoms of malaria. When we tracked temporal changes in parasite VSA expression to ask whether variants associated with severe disease rapidly expand in naive hosts, we found no transcriptional evidence to support this hypothesis. These data indicate that parasite variants that dominate severe malaria do not have an intrinsic growth or survival advantage; instead, they presumably rely upon infection-induced changes in their within-host environment for selection.<\/jats:p>","DOI":"10.7554\/elife.62800","type":"journal-article","created":{"date-parts":[[2021,3,1]],"date-time":"2021-03-01T19:00:25Z","timestamp":1614625225000},"update-policy":"https:\/\/doi.org\/10.7554\/elife.62800","source":"Crossref","is-referenced-by-count":33,"title":["Mapping immune variation and var gene switching in naive hosts infected with Plasmodium falciparum"],"prefix":"10.7554","volume":"10","author":[{"given":"Kathryn","family":"Milne","sequence":"first","affiliation":[{"name":"Institute of Immunology and Infection Research, University of Edinburgh, Edinburgh, United Kingdom"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alasdair","family":"Ivens","sequence":"additional","affiliation":[{"name":"Institute of Immunology and Infection Research, University of Edinburgh, Edinburgh, United Kingdom"},{"name":"Centre for Immunity, Infection and Evolution, University of Edinburgh, Edinburgh, United Kingdom"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Adam J","family":"Reid","sequence":"additional","affiliation":[{"name":"Wellcome Sanger Institute, Cambridge, United Kingdom"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Magda E","family":"Lotkowska","sequence":"additional","affiliation":[{"name":"Wellcome Sanger Institute, Cambridge, United Kingdom"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Aine","family":"O'Toole","sequence":"additional","affiliation":[{"name":"Centre for Immunity, Infection and Evolution, University of Edinburgh, Edinburgh, United Kingdom"},{"name":"Institute of Evolutionary Biology, University of Edinburgh, Edinburgh, United Kingdom"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Geetha","family":"Sankaranarayanan","sequence":"additional","affiliation":[{"name":"Wellcome Sanger Institute, Cambridge, United Kingdom"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Diana","family":"Munoz Sandoval","sequence":"additional","affiliation":[{"name":"Institute of Immunology and Infection Research, University of Edinburgh, Edinburgh, United Kingdom"},{"name":"Instituto de Microbiologia, Universidad San Francisco de Quito, Quito, Ecuador"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wiebke","family":"Nahrendorf","sequence":"additional","affiliation":[{"name":"Institute of Immunology and Infection Research, University of Edinburgh, Edinburgh, United Kingdom"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Clement","family":"Regnault","sequence":"additional","affiliation":[{"name":"Wellcome Centre for Integrative Parasitology, University of Glasgow, Glasgow, United Kingdom"},{"name":"Glasgow Polyomics, University of Glasgow, Glasgow, United Kingdom"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7030-7839","authenticated-orcid":true,"given":"Nick J","family":"Edwards","sequence":"additional","affiliation":[{"name":"The Jenner Institute, University of Oxford, Oxford, United Kingdom"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sarah E","family":"Silk","sequence":"additional","affiliation":[{"name":"The Jenner Institute, University of Oxford, Oxford, United Kingdom"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ruth O","family":"Payne","sequence":"additional","affiliation":[{"name":"The Jenner Institute, University of Oxford, Oxford, United Kingdom"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Angela M","family":"Minassian","sequence":"additional","affiliation":[{"name":"The Jenner Institute, University of Oxford, Oxford, United Kingdom"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Navin","family":"Venkatraman","sequence":"additional","affiliation":[{"name":"The Jenner Institute, University of Oxford, Oxford, United Kingdom"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mandy J","family":"Sanders","sequence":"additional","affiliation":[{"name":"Wellcome Sanger Institute, Cambridge, United Kingdom"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Adrian VS","family":"Hill","sequence":"additional","affiliation":[{"name":"The Jenner Institute, University of Oxford, Oxford, United Kingdom"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Michael","family":"Barrett","sequence":"additional","affiliation":[{"name":"Wellcome Centre for Integrative Parasitology, University of Glasgow, Glasgow, United Kingdom"},{"name":"Glasgow Polyomics, University of Glasgow, Glasgow, United Kingdom"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9581-0377","authenticated-orcid":true,"given":"Matthew","family":"Berriman","sequence":"additional","affiliation":[{"name":"Wellcome Sanger Institute, Cambridge, United Kingdom"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9415-1357","authenticated-orcid":true,"given":"Simon J","family":"Draper","sequence":"additional","affiliation":[{"name":"The Jenner Institute, University of Oxford, Oxford, United Kingdom"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7702-1892","authenticated-orcid":true,"given":"J Alexandra","family":"Rowe","sequence":"additional","affiliation":[{"name":"Institute of Immunology and Infection Research, University of Edinburgh, Edinburgh, United Kingdom"},{"name":"Centre for Immunity, Infection and Evolution, University of Edinburgh, Edinburgh, United Kingdom"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5506-2773","authenticated-orcid":true,"given":"Philip J","family":"Spence","sequence":"additional","affiliation":[{"name":"Institute of Immunology and Infection Research, University of Edinburgh, Edinburgh, United Kingdom"},{"name":"Centre for Immunity, Infection and Evolution, University of Edinburgh, Edinburgh, United Kingdom"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"4374","published-online":{"date-parts":[[2021,3,2]]},"reference":[{"key":"bib1","doi-asserted-by":"publisher","DOI":"10.1186\/s12879-017-2686-0","article-title":"Plasmodium falciparum malaria parasite var gene expression is modified by host antibodies: longitudinal evidence from controlled infections of kenyan adults with varying natural exposure","volume":"17","author":"Abdi","year":"2017","journal-title":"BMC Infectious Diseases"},{"key":"bib2","doi-asserted-by":"publisher","DOI":"10.1186\/s12936-017-1796-x","article-title":"Patterns of inflammatory responses and parasite tolerance vary with malaria transmission intensity","volume":"16","author":"Ademolue","year":"2017","journal-title":"Malaria Journal"},{"key":"bib3","doi-asserted-by":"publisher","first-page":"E982","DOI":"10.1073\/pnas.1420855112","article-title":"Antisense long noncoding RNAs regulate var gene activation in the malaria parasite Plasmodium falciparum","volume":"112","author":"Amit-Avraham","year":"2015","journal-title":"PNAS"},{"key":"bib4","doi-asserted-by":"publisher","first-page":"1063","DOI":"10.1073\/pnas.1712879115","article-title":"Infected erythrocytes expressing DC13 PfEMP1 differ from recombinant proteins in EPCR-binding function","volume":"115","author":"Azasi","year":"2018","journal-title":"PNAS"},{"key":"bib5","doi-asserted-by":"publisher","DOI":"10.1371\/journal.ppat.1005538","article-title":"Mosquito passage dramatically changes var gene expression in controlled human Plasmodium falciparum infections","volume":"12","author":"Bachmann","year":"2016","journal-title":"PLOS Pathogens"},{"key":"bib6","doi-asserted-by":"publisher","DOI":"10.1371\/journal.ppat.1007906","article-title":"Controlled human malaria infection with Plasmodium falciparum demonstrates impact of naturally acquired immunity on virulence gene expression","volume":"15","author":"Bachmann","year":"2019","journal-title":"PLOS Pathogens"},{"key":"bib7","doi-asserted-by":"publisher","first-page":"592","DOI":"10.1086\/517482","article-title":"Age-dependent susceptibility to severe disease with primary exposure to Plasmodium falciparum","volume":"178","author":"Baird","year":"1998","journal-title":"Journal of Infectious Diseases"},{"key":"bib8","doi-asserted-by":"publisher","first-page":"791","DOI":"10.1017\/S0950268803008422","article-title":"Adult javanese migrants to indonesian papua at high risk of severe disease caused by malaria","volume":"131","author":"Baird","year":"2003","journal-title":"Epidemiology and Infection"},{"key":"bib9","doi-asserted-by":"publisher","first-page":"776","DOI":"10.1038\/s41590-018-0121-3","article-title":"Integration of multi-omics data and deep phenotyping enables prediction of cytokine responses","volume":"19","author":"Bakker","year":"2018","journal-title":"Nature Immunology"},{"key":"bib10","doi-asserted-by":"publisher","DOI":"10.1128\/mBio.00420-19","article-title":"Binding heterogeneity of Plasmodium falciparum to engineered 3D brain microvessels is mediated by EPCR and ICAM-1","volume":"10","author":"Bernabeu","year":"2019","journal-title":"mBio"},{"key":"bib11","doi-asserted-by":"publisher","first-page":"1091","DOI":"10.1093\/bioinformatics\/btp101","article-title":"ClueGO: a cytoscape plug-in to decipher functionally grouped gene ontology and pathway annotation networks","volume":"25","author":"Bindea","year":"2009","journal-title":"Bioinformatics"},{"key":"bib12","doi-asserted-by":"publisher","DOI":"10.12688\/wellcomeopenres.15194.1","article-title":"Progression of the canonical reference malaria parasite genome from 2002-2019","volume":"4","author":"B\u00f6hme","year":"2019","journal-title":"Wellcome Open Research"},{"key":"bib13","doi-asserted-by":"publisher","first-page":"1532","DOI":"10.1016\/j.cell.2017.10.020","article-title":"Lysophosphatidylcholine regulates sexual stage differentiation in the human malaria parasite Plasmodium falciparum","volume":"171","author":"Brancucci","year":"2017","journal-title":"Cell"},{"key":"bib14","doi-asserted-by":"publisher","first-page":"525","DOI":"10.1038\/nbt.3519","article-title":"Near-optimal probabilistic RNA-seq quantification","volume":"34","author":"Bray","year":"2016","journal-title":"Nature Biotechnology"},{"key":"bib15","doi-asserted-by":"publisher","first-page":"37","DOI":"10.1016\/j.cell.2014.12.020","article-title":"Variation in the human immune system is largely driven by non-heritable influences","volume":"160","author":"Brodin","year":"2015","journal-title":"Cell"},{"key":"bib16","doi-asserted-by":"publisher","first-page":"252","DOI":"10.1086\/315652","article-title":"Plasmodium falciparum-infected erythrocytes: agglutination by diverse kenyan plasma is associated with severe disease and young host age","volume":"182","author":"Bull","year":"2000","journal-title":"The Journal of Infectious Diseases"},{"key":"bib17","doi-asserted-by":"publisher","DOI":"10.1172\/jci.insight.93434","article-title":"Dichotomous miR expression and immune responses following primary blood-stage malaria","volume":"2","author":"Burel","year":"2017","journal-title":"JCI Insight"},{"key":"bib18","doi-asserted-by":"publisher","first-page":"495","DOI":"10.4269\/ajtmh.1997.57.495","article-title":"Measurement of Plasmodium falciparum growth rates in vivo: a test of malaria vaccines","volume":"57","author":"Cheng","year":"1997","journal-title":"The American Journal of Tropical Medicine and Hygiene"},{"key":"bib19","doi-asserted-by":"publisher","first-page":"465","DOI":"10.1016\/j.biocel.2010.12.004","article-title":"Casein kinase 1: complexity in the family","volume":"43","author":"Cheong","year":"2011","journal-title":"The International Journal of Biochemistry & Cell Biology"},{"key":"bib20","doi-asserted-by":"publisher","first-page":"E1772","DOI":"10.1073\/pnas.1120461109","article-title":"A subset of group A-like var genes encodes the malaria parasite ligands for binding to human brain endothelial cells","volume":"109","author":"Claessens","year":"2012","journal-title":"PNAS"},{"key":"bib21","doi-asserted-by":"publisher","DOI":"10.1038\/srep41303","article-title":"Culture adaptation of malaria parasites selects for convergent loss-of-function mutants","volume":"7","author":"Claessens","year":"2017","journal-title":"Scientific Reports"},{"key":"bib22","doi-asserted-by":"publisher","first-page":"1048","DOI":"10.1093\/bioinformatics\/bts069","article-title":"IDEOM: an excel interface for analysis of LC-MS-based metabolomics data","volume":"28","author":"Creek","year":"2012","journal-title":"Bioinformatics"},{"key":"bib23","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0079287","article-title":"Identification of a secreted casein kinase 1 in leishmania donovani: effect of protein over expression on parasite growth and virulence","volume":"8","author":"Dan-Goor","year":"2013","journal-title":"PLOS ONE"},{"key":"bib24","doi-asserted-by":"publisher","DOI":"10.1016\/j.cyto.2019.154838","article-title":"Transforming growth factor-beta profiles correlate with clinical symptoms and parameters of haemostasis and inflammation in a controlled human malaria infection","volume":"125","author":"de Jong","year":"2020","journal-title":"Cytokine"},{"key":"bib25","doi-asserted-by":"publisher","first-page":"625","DOI":"10.1146\/annurev-micro-090816-093841","article-title":"Variant gene expression and antigenic variation by malaria parasites","volume":"71","author":"Deitsch","year":"2017","journal-title":"Annual Review of Microbiology"},{"key":"bib26","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pmed.0020204","article-title":"Estimation of the total parasite biomass in acute falciparum malaria from plasma PfHRP2","volume":"2","author":"Dondorp","year":"2005","journal-title":"PLOS Medicine"},{"key":"bib27","doi-asserted-by":"publisher","first-page":"151","DOI":"10.1086\/589287","article-title":"The relationship between age and the manifestations of and mortality associated with severe malaria","volume":"47","author":"Dondorp","year":"2008","journal-title":"Clinical Infectious Diseases"},{"key":"bib28","doi-asserted-by":"publisher","first-page":"340","DOI":"10.1093\/infdis\/jit156","article-title":"Comparison of modeling methods to determine liver-to-blood inocula and parasite multiplication rates during controlled human malaria infection","volume":"208","author":"Douglas","year":"2013","journal-title":"The Journal of Infectious Diseases"},{"key":"bib29","doi-asserted-by":"publisher","first-page":"43","DOI":"10.1016\/j.chom.2018.06.008","article-title":"Malaria vaccines: recent advances and new horizons","volume":"24","author":"Draper","year":"2018","journal-title":"Cell Host & Microbe"},{"key":"bib30","doi-asserted-by":"publisher","DOI":"10.1128\/mBio.00217-19","article-title":"Meta-analysis of Plasmodium falciparum var signatures contributing to severe malaria in african children and indian adults","volume":"10","author":"Duffy","year":"2019","journal-title":"mBio"},{"key":"bib31","doi-asserted-by":"publisher","first-page":"561","DOI":"10.4269\/ajtmh.2012.11-0504","article-title":"Controlled human blood stage malaria infection: current status and potential applications","volume":"86","author":"Duncan","year":"2012","journal-title":"The American Journal of Tropical Medicine and Hygiene"},{"key":"bib32","doi-asserted-by":"publisher","first-page":"9","DOI":"10.1016\/j.mam.2017.01.002","article-title":"Extracellular ATP and Adenosine: the yin and yang in immune responses?","volume":"55","author":"Faas","year":"2017","journal-title":"Molecular Aspects of Medicine"},{"key":"bib33","doi-asserted-by":"publisher","first-page":"33","DOI":"10.1016\/0035-9203(49)90022-X","article-title":"Blood examination and prognosis in acute falciparum malaria","volume":"43","author":"Field","year":"1949","journal-title":"Transactions of the Royal Society of Tropical Medicine and Hygiene"},{"key":"bib34","doi-asserted-by":"publisher","first-page":"D766","DOI":"10.1093\/nar\/gky955","article-title":"GENCODE reference annotation for the human and mouse genomes","volume":"47","author":"Frankish","year":"2019","journal-title":"Nucleic Acids Research"},{"key":"bib35","doi-asserted-by":"publisher","first-page":"25","DOI":"10.1016\/j.cell.2005.01.037","article-title":"Telomeric heterochromatin propagation and histone acetylation control mutually exclusive expression of antigenic variation genes in malaria parasites","volume":"121","author":"Freitas-Junior","year":"2005","journal-title":"Cell"},{"key":"bib36","doi-asserted-by":"publisher","first-page":"202","DOI":"10.1016\/S1471-4922(03)00067-9","article-title":"Switching rates of Plasmodium falciparum var genes: faster than we thought?","volume":"19","author":"Gatton","year":"2003","journal-title":"Trends in Parasitology"},{"key":"bib37","doi-asserted-by":"publisher","first-page":"467","DOI":"10.4269\/ajtmh.2002.66.467","article-title":"Evaluation of the pyrogenic threshold for Plasmodium falciparum malaria in naive individuals","volume":"66","author":"Gatton","year":"2002","journal-title":"The American Journal of Tropical Medicine and Hygiene"},{"key":"bib38","doi-asserted-by":"publisher","first-page":"1799","DOI":"10.1056\/NEJMoa1303944","article-title":"Parasite burden and severity of malaria in tanzanian children","volume":"370","author":"Gon\u00e7alves","year":"2014","journal-title":"New England Journal of Medicine"},{"key":"bib39","doi-asserted-by":"publisher","first-page":"207","DOI":"10.1038\/icb.2010.158","article-title":"CXCR3 ligands: redundant, collaborative and antagonistic functions","volume":"89","author":"Groom","year":"2011","journal-title":"Immunology & Cell Biology"},{"key":"bib40","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0010685","article-title":"Why functional pre-erythrocytic and bloodstage malaria vaccines fail: a meta-analysis of fully protective immunizations and novel immunological model","volume":"5","author":"Guilbride","year":"2010","journal-title":"PLOS ONE"},{"key":"bib41","doi-asserted-by":"publisher","first-page":"718","DOI":"10.1111\/cmi.12115","article-title":"Silence, activate, poise and switch! mechanisms of antigenic variation in Plasmodium falciparum","volume":"15","author":"Guizetti","year":"2013","journal-title":"Cellular Microbiology"},{"key":"bib42","doi-asserted-by":"publisher","first-page":"515","DOI":"10.1172\/JCI115889","article-title":"Serum cytokine profiles in experimental human malaria. relationship to protection and disease course after challenge","volume":"90","author":"Harpaz","year":"1992","journal-title":"Journal of Clinical Investigation"},{"key":"bib43","doi-asserted-by":"publisher","first-page":"11129","DOI":"10.1073\/pnas.0402347101","article-title":"Variable var transition rates underlie antigenic variation in malaria","volume":"101","author":"Horrocks","year":"2004","journal-title":"PNAS"},{"key":"bib44","doi-asserted-by":"publisher","first-page":"4090","DOI":"10.1128\/IAI.65.10.4090-4093.1997","article-title":"Rapid reemergence of T cells into peripheral circulation following treatment of severe and uncomplicated Plasmodium falciparum malaria","volume":"65","author":"Hviid","year":"1997","journal-title":"Infection and Immunity"},{"key":"bib45","doi-asserted-by":"publisher","first-page":"1179","DOI":"10.1084\/jem.20040274","article-title":"Plasmodium falciparum associated with severe childhood malaria preferentially expresses PfEMP1 encoded by group A var genes","volume":"199","author":"Jensen","year":"2004","journal-title":"Journal of Experimental Medicine"},{"key":"bib46","doi-asserted-by":"publisher","first-page":"230","DOI":"10.1111\/imr.12807","article-title":"Cerebral Plasmodium falciparum malaria: the role of PfEMP1 in its pathogenesis and immunity, and PfEMP1-based vaccines to prevent it","volume":"293","author":"Jensen","year":"2020","journal-title":"Immunological Reviews"},{"key":"bib47","doi-asserted-by":"publisher","first-page":"839","DOI":"10.15252\/emmm.201606188","article-title":"Plasmodium falciparum var genes expressed in children with severe malaria encode cidr\u03b11 domains","volume":"8","author":"Jespersen","year":"2016","journal-title":"EMBO Molecular Medicine"},{"key":"bib48","doi-asserted-by":"publisher","DOI":"10.1186\/s12964-018-0236-z","article-title":"Casein kinase 1\u03b1: biological mechanisms and theranostic potential","volume":"16","author":"Jiang","year":"2018","journal-title":"Cell Communication and Signaling"},{"key":"bib49","doi-asserted-by":"publisher","first-page":"357","DOI":"10.1038\/nmeth.3317","article-title":"HISAT: a fast spliced aligner with low memory requirements","volume":"12","author":"Kim","year":"2015","journal-title":"Nature Methods"},{"key":"bib50","doi-asserted-by":"publisher","first-page":"311","DOI":"10.1016\/S0166-6851(99)00193-0","article-title":"A simple RNA analysis method shows var and rif multigene family expression patterns in Plasmodium falciparum","volume":"105","author":"Kyes","year":"2000","journal-title":"Molecular and Biochemical Parasitology"},{"key":"bib51","doi-asserted-by":"publisher","first-page":"211","DOI":"10.1016\/j.molbiopara.2006.08.005","article-title":"Differential var gene transcription in Plasmodium falciparum isolates from patients with cerebral malaria compared to hyperparasitaemia","volume":"150","author":"Kyriacou","year":"2006","journal-title":"Molecular and Biochemical Parasitology"},{"key":"bib52","doi-asserted-by":"publisher","DOI":"10.1186\/1475-2875-4-21","article-title":"Expression of Plasmodium falciparum erythrocyte membrane protein 1 in experimentally infected humans","volume":"4","author":"Lavstsen","year":"2005","journal-title":"Malaria Journal"},{"key":"bib53","doi-asserted-by":"publisher","first-page":"E1791","DOI":"10.1073\/pnas.1120455109","article-title":"Plasmodium falciparum erythrocyte membrane protein 1 domain cassettes 8 and 13 are associated with severe malaria in children","volume":"109","author":"Lavstsen","year":"2012","journal-title":"PNAS"},{"key":"bib54","doi-asserted-by":"publisher","first-page":"403","DOI":"10.1016\/j.chom.2017.02.009","article-title":"Structure-Guided identification of a family of dual Receptor-Binding PfEMP1 that is associated with cerebral malaria","volume":"21","author":"Lennartz","year":"2017","journal-title":"Cell Host & Microbe"},{"key":"bib55","doi-asserted-by":"publisher","first-page":"1099","DOI":"10.1016\/j.cell.2016.10.017","article-title":"A functional genomics approach to understand variation in cytokine production in humans","volume":"167","author":"Li","year":"2016","journal-title":"Cell"},{"key":"bib56","doi-asserted-by":"publisher","first-page":"6401","DOI":"10.1128\/MCB.00478-09","article-title":"Mammalian casein kinase 1alpha and its leishmanial ortholog regulate stability of IFNAR1 and type I interferon signaling","volume":"29","author":"Liu","year":"2009","journal-title":"Molecular and Cellular Biology"},{"key":"bib57","doi-asserted-by":"publisher","DOI":"10.1186\/s13059-014-0550-8","article-title":"Moderated estimation of fold change and dispersion for RNA-seq data with DESeq2","volume":"15","author":"Love","year":"2014","journal-title":"Genome Biology"},{"key":"bib58","doi-asserted-by":"publisher","first-page":"1385","DOI":"10.1098\/rstb.1997.0124","article-title":"Host-parasite interaction and morbidity in malaria endemic Areas","volume":"352","author":"Marsh","year":"1997","journal-title":"Philosophical Transactions of the Royal Society of London. Series B: Biological Sciences"},{"key":"bib59","doi-asserted-by":"publisher","first-page":"936","DOI":"10.1126\/science.1214935","article-title":"Disease tolerance as a defense strategy","volume":"335","author":"Medzhitov","year":"2012","journal-title":"Science"},{"key":"bib60","doi-asserted-by":"publisher","first-page":"228","DOI":"10.1126\/scitranslmed.3007240","article-title":"Functional network pipeline reveals genetic determinants associated with in situ lymphocyte proliferation and survival of Cancer patients","volume":"6","author":"Mlecnik","year":"2014","journal-title":"Science Translational Medicine"},{"key":"bib61","doi-asserted-by":"publisher","first-page":"205","DOI":"10.1016\/S0035-9203(02)90308-1","article-title":"Malaria therapy reinoculation data suggest individual variation of an innate immune response and independent acquisition of antiparasitic and antitoxic immunities","volume":"96","author":"Molineaux","year":"2002","journal-title":"Transactions of the Royal Society of Tropical Medicine and Hygiene"},{"key":"bib62","doi-asserted-by":"publisher","first-page":"399","DOI":"10.1016\/j.celrep.2016.09.015","article-title":"Type I interferons regulate immune responses in humans with Blood-Stage Plasmodium falciparum infection","volume":"17","author":"Montes de Oca","year":"2016","journal-title":"Cell Reports"},{"key":"bib63","doi-asserted-by":"publisher","DOI":"10.1186\/s13073-019-0708-9","article-title":"Strains used in whole organism Plasmodium falciparum vaccine trials differ in genome structure, sequence, and immunogenic potential","volume":"12","author":"Moser","year":"2020","journal-title":"Genome Medicine"},{"key":"bib64","doi-asserted-by":"publisher","first-page":"5561","DOI":"10.1128\/IAI.00408-06","article-title":"Common and divergent immune response signaling pathways discovered in peripheral blood mononuclear cell gene expression patterns in Presymptomatic and clinically apparent malaria","volume":"74","author":"Ockenhouse","year":"2006","journal-title":"Infection and Immunity"},{"key":"bib65","doi-asserted-by":"publisher","first-page":"302","DOI":"10.1038\/s41590-018-0049-7","article-title":"Natural variation in the parameters of innate immune cells is preferentially driven by genetic factors","volume":"19","author":"Patin","year":"2018","journal-title":"Nature Immunology"},{"key":"bib66","doi-asserted-by":"publisher","first-page":"1743","DOI":"10.1093\/infdis\/jiw039","article-title":"Demonstration of the Blood-Stage Plasmodium falciparum controlled human malaria infection model to assess efficacy of the P. falciparum apical membrane antigen 1 vaccine, FMP2.1\/AS01","volume":"213","author":"Payne","year":"2016","journal-title":"Journal of Infectious Diseases"},{"key":"bib67","doi-asserted-by":"publisher","first-page":"10689","DOI":"10.1073\/pnas.162349899","article-title":"High diversity and rapid changeover of expressed var genes during the acute phase of Plasmodium falciparum infections in human volunteers","volume":"99","author":"Peters","year":"2002","journal-title":"PNAS"},{"key":"bib68","doi-asserted-by":"publisher","first-page":"E488","DOI":"10.1073\/pnas.1714765115","article-title":"Distinctive roles of age, sex, and genetics in shaping transcriptional variation of human immune responses to microbial challenges","volume":"115","author":"Piasecka","year":"2018","journal-title":"PNAS"},{"key":"bib69","doi-asserted-by":"publisher","first-page":"1096","DOI":"10.1038\/nmeth.2639","article-title":"Smart-seq2 for sensitive full-length transcriptome profiling in single cells","volume":"10","author":"Picelli","year":"2013","journal-title":"Nature Methods"},{"key":"bib70","doi-asserted-by":"publisher","DOI":"10.1371\/journal.ppat.1004079","article-title":"Exposure-dependent control of malaria-induced inflammation in children","volume":"10","author":"Portugal","year":"2014","journal-title":"PLOS Pathogens"},{"key":"bib71","doi-asserted-by":"publisher","first-page":"841","DOI":"10.1093\/bioinformatics\/btq033","article-title":"BEDTools: a flexible suite of utilities for comparing genomic features","volume":"26","author":"Quinlan","year":"2010","journal-title":"Bioinformatics"},{"key":"bib72","doi-asserted-by":"publisher","first-page":"48","DOI":"10.1016\/j.autneu.2015.04.007","article-title":"Purinergic transmission in blood vessels","volume":"191","author":"Ralevic","year":"2015","journal-title":"Autonomic Neuroscience"},{"key":"bib73","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pcbi.1000933","article-title":"Plasmodium falciparum erythrocyte membrane protein 1 diversity in seven genomes--divide and conquer","volume":"6","author":"Rask","year":"2010","journal-title":"PLOS Computational Biology"},{"key":"bib74","doi-asserted-by":"publisher","DOI":"10.7554\/eLife.33105","article-title":"Single-cell RNA-seq reveals hidden transcriptional variation in malaria parasites","volume":"7","author":"Reid","year":"2018","journal-title":"eLife"},{"key":"bib75","doi-asserted-by":"publisher","first-page":"689","DOI":"10.1038\/357689a0","article-title":"Rapid switching to multiple antigenic and adhesive phenotypes in malaria","volume":"357","author":"Roberts","year":"1992","journal-title":"Nature"},{"key":"bib76","doi-asserted-by":"publisher","first-page":"139","DOI":"10.1093\/bioinformatics\/btp616","article-title":"edgeR: a bioconductor package for differential expression analysis of digital gene expression data","volume":"26","author":"Robinson","year":"2010","journal-title":"Bioinformatics"},{"key":"bib77","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0038434","article-title":"Comparison of clinical and parasitological data from controlled human malaria infection trials","volume":"7","author":"Roestenberg","year":"2012","journal-title":"PLOS ONE"},{"key":"bib78","doi-asserted-by":"publisher","first-page":"306","DOI":"10.1016\/j.cell.2018.10.041","article-title":"Oligopeptide signaling through TbGPR89 drives trypanosome quorum sensing","volume":"176","author":"Rojas","year":"2019","journal-title":"Cell"},{"key":"bib79","doi-asserted-by":"publisher","DOI":"10.1101\/cshperspect.a029421","article-title":"Do memory CD4 T cells keep their Cell-Type programming: plasticity versus fate commitment? T-Cell heterogeneity, plasticity, and selection in humans","volume":"10","author":"Sallusto","year":"2018","journal-title":"Cold Spring Harbor Perspectives in Biology"},{"key":"bib80","doi-asserted-by":"publisher","first-page":"2786","DOI":"10.1021\/ac2000994","article-title":"PeakML\/mzMatch: a file format, Java library, R library, and tool-chain for mass spectrometry data analysis","volume":"83","author":"Scheltema","year":"2011","journal-title":"Analytical Chemistry"},{"key":"bib81","doi-asserted-by":"publisher","first-page":"2355","DOI":"10.1038\/mt.2012.223","article-title":"ChAd63-MVA-vectored blood-stage malaria vaccines targeting MSP1 and AMA1: assessment of efficacy against mosquito bite challenge in humans","volume":"20","author":"Sheehy","year":"2012","journal-title":"Molecular Therapy"},{"key":"bib82","doi-asserted-by":"publisher","first-page":"779","DOI":"10.1021\/ac051437y","article-title":"XCMS: processing mass spectrometry data for metabolite profiling using nonlinear peak alignment, matching, and identification","volume":"78","author":"Smith","year":"2006","journal-title":"Analytical Chemistry"},{"key":"bib83","doi-asserted-by":"publisher","first-page":"1976","DOI":"10.1111\/cmi.12183","article-title":"Malaria's deadly grip: cytoadhesion of Plasmodium falciparum-infected erythrocytes","volume":"15","author":"Smith","year":"2013","journal-title":"Cellular Microbiology"},{"key":"bib84","doi-asserted-by":"publisher","DOI":"10.1371\/journal.ppat.1005975","article-title":"STING-Licensed macrophages prime type I IFN production by plasmacytoid dendritic cells in the bone marrow during severe plasmodium yoelii malaria","volume":"12","author":"Spaulding","year":"2016","journal-title":"PLOS Pathogens"},{"key":"bib85","doi-asserted-by":"publisher","first-page":"228","DOI":"10.1038\/nature12231","article-title":"Vector transmission regulates immune control of plasmodium virulence","volume":"498","author":"Spence","year":"2013","journal-title":"Nature"},{"key":"bib86","doi-asserted-by":"publisher","DOI":"10.1186\/s12936-015-0663-x","article-title":"Development of cultured Plasmodium falciparum blood-stage malaria cell banks for early phase in vivo clinical trial assessment of anti-malaria drugs and vaccines","volume":"14","author":"Stanisic","year":"2015","journal-title":"Malaria Journal"},{"key":"bib87","doi-asserted-by":"publisher","DOI":"10.1128\/IAI.00479-17","article-title":"Controlled human malaria infection: applications, advances, and challenges","volume":"86","author":"Stanisic","year":"2018","journal-title":"Infection and Immunity"},{"key":"bib88","doi-asserted-by":"publisher","first-page":"211","DOI":"10.1007\/s11306-007-0082-2","article-title":"Proposed minimum reporting standards for chemical analysis chemical analysis working group (CAWG) Metabolomics standards initiative (MSI)","volume":"3","author":"Sumner","year":"2007","journal-title":"Metabolomics"},{"key":"bib89","doi-asserted-by":"publisher","first-page":"1111","DOI":"10.1016\/j.cell.2016.10.018","article-title":"Host and environmental factors influencing individual human cytokine responses","volume":"167","author":"Ter Horst","year":"2016","journal-title":"Cell"},{"key":"bib90","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pbio.2004328","article-title":"The Plasmodium falciparum transcriptome in severe malaria reveals altered expression of genes involved in important processes including surface antigen-encoding var genes","volume":"16","author":"Tonkin-Hill","year":"2018","journal-title":"PLOS Biology"},{"key":"bib91","doi-asserted-by":"publisher","DOI":"10.1038\/srep31291","article-title":"Transcriptomic evidence for modulation of host inflammatory responses during febrile Plasmodium falciparum malaria","volume":"6","author":"Tran","year":"2016","journal-title":"Scientific Reports"},{"key":"bib92","doi-asserted-by":"publisher","DOI":"10.1038\/s41598-019-44924-7","article-title":"Whole-blood transcriptomic signatures induced during immunization by chloroquine prophylaxis and Plasmodium falciparum sporozoites","volume":"9","author":"Tran","year":"2019","journal-title":"Scientific Reports"},{"key":"bib93","doi-asserted-by":"publisher","first-page":"502","DOI":"10.1038\/nature12216","article-title":"Severe malaria is associated with parasite binding to endothelial protein C receptor","volume":"498","author":"Turner","year":"2013","journal-title":"Nature"},{"key":"bib94","doi-asserted-by":"publisher","DOI":"10.1186\/1471-2164-7-142","article-title":"Centering, scaling, and transformations: improving the biological information content of metabolomics data","volume":"7","author":"van den Berg","year":"2006","journal-title":"BMC Genomics"},{"key":"bib95","doi-asserted-by":"publisher","first-page":"287","DOI":"10.1016\/j.immuni.2005.08.006","article-title":"Upregulation of TGF-beta, FOXP3, and CD4+CD25+ regulatory T cells correlates with more rapid parasite growth in human malaria infection","volume":"23","author":"Walther","year":"2005","journal-title":"Immunity"},{"key":"bib96","doi-asserted-by":"publisher","first-page":"5736","DOI":"10.4049\/jimmunol.177.8.5736","article-title":"Innate immune responses to human malaria: heterogeneous cytokine responses to blood-stage Plasmodium falciparum correlate with parasitological and clinical outcomes","volume":"177","author":"Walther","year":"2006","journal-title":"The Journal of Immunology"},{"key":"bib97","doi-asserted-by":"publisher","first-page":"478","DOI":"10.1016\/j.parint.2009.07.004","article-title":"The Plasmodium falciparum var gene transcription strategy at the onset of blood stage infection in a human volunteer","volume":"58","author":"Wang","year":"2009","journal-title":"Parasitology International"},{"key":"bib98","doi-asserted-by":"publisher","first-page":"90","DOI":"10.1016\/j.ejop.2016.07.006","article-title":"Targeted disruption of CK1\u03b1 in Toxoplasma gondii increases acute virulence in mice","volume":"56","author":"Wang","year":"2016","journal-title":"European Journal of Protistology"},{"key":"bib99","doi-asserted-by":"publisher","first-page":"129","DOI":"10.1126\/scitranslmed.3003247","article-title":"Prognostic indicators of Life-Threatening malaria are associated with distinct parasite variant antigen profiles","volume":"4","author":"Warimwe","year":"2012","journal-title":"Science Translational Medicine"},{"key":"bib100","doi-asserted-by":"publisher","first-page":"69","DOI":"10.1007\/978-1-4939-7737-6_5","article-title":"EuPathDB: the eukaryotic pathogen genomics database resource","volume":"1757","author":"Warrenfeltz","year":"2018","journal-title":"Methods in Molecular Biology"},{"key":"bib101","doi-asserted-by":"publisher","first-page":"1618","DOI":"10.1128\/EC.00229-07","article-title":"Choline induces transcriptional repression and proteasomal degradation of the malarial phosphoethanolamine methyltransferase","volume":"6","author":"Witola","year":"2007","journal-title":"Eukaryotic Cell"},{"key":"bib102","doi-asserted-by":"publisher","first-page":"253","DOI":"10.1111\/imr.12811","article-title":"Fast and fierce versus slow and smooth: heterogeneity in immune responses to plasmodium in the controlled human malaria infection model","volume":"293","author":"Yap","year":"2020","journal-title":"Immunological Reviews"},{"key":"bib103","doi-asserted-by":"publisher","DOI":"10.1186\/s12936-015-0565-y","article-title":"Transcription of the var genes from a freshly-obtained field isolate of Plasmodium falciparum shows more variable switching patterns than long laboratory-adapted isolates","volume":"14","author":"Ye","year":"2015","journal-title":"Malaria Journal"},{"key":"bib104","doi-asserted-by":"publisher","first-page":"17097","DOI":"10.1073\/pnas.0805782105","article-title":"Angiopoietin-2 is associated with decreased endothelial nitric oxide and poor clinical outcome in severe falciparum malaria","volume":"105","author":"Yeo","year":"2008","journal-title":"PNAS"},{"key":"bib105","doi-asserted-by":"publisher","first-page":"1093","DOI":"10.1016\/j.immuni.2016.10.001","article-title":"Cross-Regulation of two type I interferon signaling pathways in plasmacytoid dendritic cells controls Anti-malaria immunity and host mortality","volume":"45","author":"Yu","year":"2016","journal-title":"Immunity"}],"container-title":["eLife"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/cdn.elifesciences.org\/articles\/62800\/elife-62800-v1.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/cdn.elifesciences.org\/articles\/62800\/elife-62800-v1.xml","content-type":"application\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/elifesciences.org\/articles\/62800","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,10,11]],"date-time":"2023-10-11T21:03:50Z","timestamp":1697058230000},"score":1,"resource":{"primary":{"URL":"https:\/\/elifesciences.org\/articles\/62800"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2021,3,2]]},"references-count":105,"alternative-id":["10.7554\/eLife.62800"],"URL":"https:\/\/doi.org\/10.7554\/elife.62800","archive":["CLOCKSS"],"relation":{"is-supplemented-by":[{"id-type":"accession","id":"GSE132050","asserted-by":"subject"},{"id-type":"accession","id":"EGAS00001003766","asserted-by":"subject"},{"id-type":"accession","id":"PRJEB33557","asserted-by":"subject"},{"id-type":"accession","id":"MTBLS1188","asserted-by":"subject"}],"has-review":[{"id-type":"doi","id":"10.7554\/eLife.62800.sa1","asserted-by":"object"},{"id-type":"doi","id":"10.7554\/eLife.62800.sa2","asserted-by":"object"}],"has-preprint":[{"id-type":"doi","id":"10.1101\/2020.09.04.20188144","asserted-by":"object"}]},"ISSN":["2050-084X"],"issn-type":[{"value":"2050-084X","type":"electronic"}],"subject":[],"published":{"date-parts":[[2021,3,2]]},"article-number":"e62800"}}