{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,27]],"date-time":"2026-09-27T12:30:34Z","timestamp":1790512234688,"version":"4.1.0"},"reference-count":68,"publisher":"Wiley","issue":"6","license":[{"start":{"date-parts":[[2020,6,18]],"date-time":"2020-06-18T00:00:00Z","timestamp":1592438400000},"content-version":"vor","delay-in-days":169,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100000925","name":"National Health and Medical Research Council","doi-asserted-by":"publisher","award":["141632"],"award-info":[{"award-number":["141632"]}],"id":[{"id":"10.13039\/501100000925","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100000925","name":"National Health and Medical Research Council","doi-asserted-by":"publisher","award":["1135955"],"award-info":[{"award-number":["1135955"]}],"id":[{"id":"10.13039\/501100000925","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100000925","name":"National Health and Medical Research Council","doi-asserted-by":"publisher","award":["1037304"],"award-info":[{"award-number":["1037304"]}],"id":[{"id":"10.13039\/501100000925","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100000925","name":"National Health and Medical Research Council","doi-asserted-by":"publisher","award":["1092789"],"award-info":[{"award-number":["1092789"]}],"id":[{"id":"10.13039\/501100000925","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100000925","name":"National Health and Medical Research Council","doi-asserted-by":"publisher","award":["1132975"],"award-info":[{"award-number":["1132975"]}],"id":[{"id":"10.13039\/501100000925","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100000925","name":"National Health and Medical Research Council","doi-asserted-by":"publisher","award":["1045156"],"award-info":[{"award-number":["1045156"]}],"id":[{"id":"10.13039\/501100000925","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100000925","name":"National Health and Medical Research Council","doi-asserted-by":"publisher","award":["1125656"],"award-info":[{"award-number":["1125656"]}],"id":[{"id":"10.13039\/501100000925","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100000925","name":"National Health and Medical Research Council","doi-asserted-by":"publisher","award":["1042072"],"award-info":[{"award-number":["1042072"]}],"id":[{"id":"10.13039\/501100000925","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100000925","name":"National Health and Medical Research Council","doi-asserted-by":"publisher","award":["1154265"],"award-info":[{"award-number":["1154265"]}],"id":[{"id":"10.13039\/501100000925","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100000925","name":"National Health and Medical Research Council","doi-asserted-by":"publisher","award":["APP5121190"],"award-info":[{"award-number":["APP5121190"]}],"id":[{"id":"10.13039\/501100000925","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001075","name":"Channel 7 Children's Research Foundation","doi-asserted-by":"publisher","award":["151016"],"award-info":[{"award-number":["151016"]}],"id":[{"id":"10.13039\/501100001075","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Clin & Trans Imm"],"published-print":{"date-parts":[[2020,1]]},"abstract":"Abstract<\/jats:title>Objectives<\/jats:title>Malaria, caused by Plasmodium<\/jats:italic> infection, remains a major global health problem. Monocytes are integral to the immune response, yet their transcriptional and functional responses in primary Plasmodium falciparum<\/jats:italic> infection and in clinical malaria are poorly understood.<\/jats:p><\/jats:sec>Methods<\/jats:title>The transcriptional and functional profiles of monocytes were examined in controlled human malaria infection with P.\u00a0falciparum<\/jats:italic> blood stages and in children and adults with acute malaria. Monocyte gene expression and functional phenotypes were examined by RNA sequencing and flow cytometry at peak infection and compared to pre\u2010infection or at convalescence in acute malaria.<\/jats:p><\/jats:sec>Results<\/jats:title>In subpatent primary infection, the monocyte transcriptional profile was dominated by an interferon (IFN) molecular signature. Pathways enriched included type I IFN signalling, innate immune response and cytokine\u2010mediated signalling. Monocytes increased TNF and IL\u201012 production upon in vitro<\/jats:italic> toll\u2010like receptor stimulation and increased IL\u201010 production upon in vitro<\/jats:italic> parasite restimulation. Longitudinal phenotypic analyses revealed sustained significant changes in the composition of monocytes following infection, with increased CD14+<\/jats:sup>CD16\u2212<\/jats:sup> and decreased CD14\u2212<\/jats:sup>CD16+<\/jats:sup> subsets. In acute malaria, monocyte CD64\/Fc\u03b3RI expression was significantly increased in children and adults, while HLA\u2010DR remained stable. Although children and adults showed a similar pattern of differentially expressed genes, the number and magnitude of gene expression change were greater in children.<\/jats:p><\/jats:sec>Conclusions<\/jats:title>Monocyte activation during subpatent malaria is driven by an IFN molecular signature with robust activation of genes enriched in pathogen detection, phagocytosis, antimicrobial activity and antigen presentation. The greater magnitude of transcriptional changes in children with acute malaria suggests monocyte phenotypes may change with age or exposure.<\/jats:p><\/jats:sec>","DOI":"10.1002\/cti2.1144","type":"journal-article","created":{"date-parts":[[2020,6,19]],"date-time":"2020-06-19T00:21:02Z","timestamp":1592526062000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":24,"title":["Transcriptional profiling and immunophenotyping show sustained activation of blood monocytes in subpatent Plasmodium falciparum<\/i> infection"],"prefix":"10.1002","volume":"9","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-2253-1577","authenticated-orcid":false,"given":"Jessica R","family":"Loughland","sequence":"first","affiliation":[{"name":"QIMR Berghofer Medical Research Institute Brisbane QLD Australia"},{"name":"Menzies School of Health Research Darwin NT Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9538-4788","authenticated-orcid":false,"given":"Tonia","family":"Woodberry","sequence":"additional","affiliation":[{"name":"Menzies School of Health Research Darwin NT Australia"},{"name":"Charles Darwin University Darwin NT Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0788-6513","authenticated-orcid":false,"given":"Matt","family":"Field","sequence":"additional","affiliation":[{"name":"Australian Institute of Tropical Health and Medicine and Centre for Tropical Bioinformatics and Molecular Biology James Cook University Cairns QLD Australia"},{"name":"John Curtin School of Medical Research Australian National University Canberra ACT Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dean W","family":"Andrew","sequence":"additional","affiliation":[{"name":"QIMR Berghofer Medical Research Institute Brisbane QLD Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Arya","family":"SheelaNair","sequence":"additional","affiliation":[{"name":"QIMR Berghofer Medical Research Institute Brisbane QLD Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nicholas L","family":"Dooley","sequence":"additional","affiliation":[{"name":"QIMR Berghofer Medical Research Institute Brisbane QLD Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kim A","family":"Piera","sequence":"additional","affiliation":[{"name":"Menzies School of Health Research Darwin NT Australia"},{"name":"Charles Darwin University Darwin NT Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Fiona H","family":"Amante","sequence":"additional","affiliation":[{"name":"QIMR Berghofer Medical Research Institute Brisbane QLD Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Enny","family":"Kenangalem","sequence":"additional","affiliation":[{"name":"Timika Malaria Research Program Papuan Health and Community Development Foundation Timika Indonesia"},{"name":"District Health Authority Timika Indonesia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ric N","family":"Price","sequence":"additional","affiliation":[{"name":"Menzies School of Health Research Darwin NT Australia"},{"name":"Charles Darwin University Darwin NT Australia"},{"name":"Centre for Tropical Medicine and Global Health Nuffield Department of Clinical Medicine University of Oxford Oxford UK"},{"name":"Mahidol\u2010Oxford Tropical Medicine Research Unit Faculty of Tropical Medicine Mahidol University Bangkok Thailand"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2813-4804","authenticated-orcid":false,"given":"Christian R","family":"Engwerda","sequence":"additional","affiliation":[{"name":"QIMR Berghofer Medical Research Institute Brisbane QLD Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nicholas M","family":"Anstey","sequence":"additional","affiliation":[{"name":"Menzies School of Health Research Darwin NT Australia"},{"name":"Charles Darwin University Darwin NT Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6596-9718","authenticated-orcid":false,"given":"James S","family":"McCarthy","sequence":"additional","affiliation":[{"name":"QIMR Berghofer Medical Research Institute Brisbane QLD Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0268-232X","authenticated-orcid":false,"given":"Michelle J","family":"Boyle","sequence":"additional","affiliation":[{"name":"QIMR Berghofer Medical Research Institute Brisbane QLD Australia"},{"name":"Menzies School of Health Research Darwin NT Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5158-7700","authenticated-orcid":false,"given":"Gabriela","family":"Minigo","sequence":"additional","affiliation":[{"name":"Menzies School of Health Research Darwin NT Australia"},{"name":"Charles Darwin University Darwin NT Australia"},{"name":"College of Health and Human Sciences Charles Darwin University Darwin NT Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2020,6,18]]},"reference":[{"key":"e_1_2_8_2_1","volume-title":"World Malaria Report","author":"WHO","year":"2019"},{"key":"e_1_2_8_3_1","doi-asserted-by":"publisher","DOI":"10.7554\/eLife.35832"},{"key":"e_1_2_8_4_1","doi-asserted-by":"publisher","DOI":"10.3389\/fimmu.2018.02888"},{"key":"e_1_2_8_5_1","doi-asserted-by":"publisher","DOI":"10.1111\/imr.12830"},{"key":"e_1_2_8_6_1","doi-asserted-by":"publisher","DOI":"10.7150\/ijms.5.1"},{"key":"e_1_2_8_7_1","doi-asserted-by":"publisher","DOI":"10.1128\/IAI.00923-13"},{"key":"e_1_2_8_8_1","doi-asserted-by":"publisher","DOI":"10.1038\/nri3742"},{"key":"e_1_2_8_9_1","doi-asserted-by":"publisher","DOI":"10.1186\/s12916-015-0391-7"},{"key":"e_1_2_8_10_1","first-page":"126","article-title":"Toll\u2010like receptors and malaria\u2010sensing and susceptibility","volume":"2","author":"Eriksson E","year":"2013","journal-title":"J Trop Dis"},{"key":"e_1_2_8_11_1","doi-asserted-by":"publisher","DOI":"10.1111\/pim.12319"},{"key":"e_1_2_8_12_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.pt.2012.10.002"},{"key":"e_1_2_8_13_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0035-9203(98)90951-8"},{"key":"e_1_2_8_14_1","doi-asserted-by":"publisher","DOI":"10.1182\/blood-2010-02-258558"},{"key":"e_1_2_8_15_1","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0176460"},{"key":"e_1_2_8_16_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.immuni.2010.08.012"},{"key":"e_1_2_8_17_1","doi-asserted-by":"publisher","DOI":"10.1172\/jci.insight.95352"},{"key":"e_1_2_8_18_1","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0162132"},{"key":"e_1_2_8_19_1","doi-asserted-by":"publisher","DOI":"10.1086\/518443"},{"key":"e_1_2_8_20_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.immuni.2019.08.009"},{"key":"e_1_2_8_21_1","doi-asserted-by":"publisher","DOI":"10.7554\/eLife.29156"},{"key":"e_1_2_8_22_1","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.0813177106"},{"key":"e_1_2_8_23_1","doi-asserted-by":"publisher","DOI":"10.1111\/imr.12811"},{"key":"e_1_2_8_24_1","doi-asserted-by":"publisher","DOI":"10.1093\/infdis\/jiy555"},{"key":"e_1_2_8_25_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00011-013-0632-1"},{"key":"e_1_2_8_26_1","doi-asserted-by":"publisher","DOI":"10.4049\/jimmunol.182.2.1107"},{"key":"e_1_2_8_27_1","doi-asserted-by":"publisher","DOI":"10.1038\/nri3070"},{"key":"e_1_2_8_28_1","doi-asserted-by":"publisher","DOI":"10.1016\/S1074-7613(03)00174-2"},{"key":"e_1_2_8_29_1","doi-asserted-by":"publisher","DOI":"10.1002\/jlb.67.1.2"},{"key":"e_1_2_8_30_1","doi-asserted-by":"publisher","DOI":"10.1182\/blood.V96.9.3231"},{"key":"e_1_2_8_31_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.immuni.2016.07.006"},{"key":"e_1_2_8_32_1","doi-asserted-by":"publisher","DOI":"10.1038\/srep29151"},{"key":"e_1_2_8_33_1","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M111.327031"},{"key":"e_1_2_8_34_1","doi-asserted-by":"publisher","DOI":"10.1038\/srep31291"},{"key":"e_1_2_8_35_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41598-017-02096-2"},{"key":"e_1_2_8_36_1","doi-asserted-by":"publisher","DOI":"10.1128\/IAI.00408-06"},{"key":"e_1_2_8_37_1","doi-asserted-by":"publisher","DOI":"10.1086\/429297"},{"key":"e_1_2_8_38_1","doi-asserted-by":"publisher","DOI":"10.1126\/scitranslmed.aar3619"},{"key":"e_1_2_8_39_1","doi-asserted-by":"publisher","DOI":"10.1186\/s12920-019-0599-z"},{"key":"e_1_2_8_40_1","doi-asserted-by":"publisher","DOI":"10.4049\/jimmunol.179.1.162"},{"key":"e_1_2_8_41_1","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.0809742106"},{"key":"e_1_2_8_42_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.celrep.2016.09.015"},{"key":"e_1_2_8_43_1","doi-asserted-by":"publisher","DOI":"10.4049\/jimmunol.172.4.2147"},{"key":"e_1_2_8_44_1","doi-asserted-by":"publisher","DOI":"10.1161\/01.ATV.0000122853.99978.b1"},{"key":"e_1_2_8_45_1","doi-asserted-by":"publisher","DOI":"10.1002\/eji.201747032"},{"key":"e_1_2_8_46_1","doi-asserted-by":"publisher","DOI":"10.1186\/1741-7015-12-108"},{"key":"e_1_2_8_47_1","doi-asserted-by":"publisher","DOI":"10.1128\/IAI.00473-15"},{"key":"e_1_2_8_48_1","doi-asserted-by":"publisher","DOI":"10.4049\/jimmunol.1302960"},{"key":"e_1_2_8_49_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41591-018-0117-4"},{"key":"e_1_2_8_50_1","doi-asserted-by":"publisher","DOI":"10.7554\/eLife.04232"},{"key":"e_1_2_8_51_1","doi-asserted-by":"publisher","DOI":"10.1128\/IAI.01522-15"},{"key":"e_1_2_8_52_1","doi-asserted-by":"publisher","DOI":"10.1084\/jem.20121972"},{"key":"e_1_2_8_53_1","doi-asserted-by":"publisher","DOI":"10.1182\/blood.V90.9.3245"},{"key":"e_1_2_8_54_1","doi-asserted-by":"publisher","DOI":"10.1126\/science.aaf1098"},{"key":"e_1_2_8_55_1","doi-asserted-by":"publisher","DOI":"10.1084\/jem.20170355"},{"key":"e_1_2_8_56_1","doi-asserted-by":"publisher","DOI":"10.4049\/jimmunol.1701010"},{"key":"e_1_2_8_57_1","doi-asserted-by":"publisher","DOI":"10.1093\/ofid\/ofz296"},{"key":"e_1_2_8_58_1","doi-asserted-by":"publisher","DOI":"10.3389\/fcimb.2019.00235"},{"key":"e_1_2_8_59_1","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.1708383114"},{"key":"e_1_2_8_60_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jcrc.2011.06.013"},{"key":"e_1_2_8_61_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.pharmthera.2017.02.043"},{"key":"e_1_2_8_62_1","doi-asserted-by":"publisher","DOI":"10.1186\/1475-2875-10-48"},{"key":"e_1_2_8_63_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0140-6736(07)60160-3"},{"key":"e_1_2_8_64_1","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0143199"},{"key":"e_1_2_8_65_1","doi-asserted-by":"publisher","DOI":"10.1093\/bioinformatics\/bts635"},{"key":"e_1_2_8_66_1","doi-asserted-by":"publisher","DOI":"10.1093\/bioinformatics\/btp352"},{"key":"e_1_2_8_67_1","doi-asserted-by":"publisher","DOI":"10.1093\/bioinformatics\/btu638"},{"key":"e_1_2_8_68_1","doi-asserted-by":"publisher","DOI":"10.1186\/s13059-014-0550-8"},{"key":"e_1_2_8_69_1","doi-asserted-by":"publisher","DOI":"10.1093\/nar\/gky1131"}],"container-title":["Clinical & Translational Immunology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/api.wiley.com\/onlinelibrary\/tdm\/v1\/articles\/10.1002%2Fcti2.1144","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/cti2.1144","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/full-xml\/10.1002\/cti2.1144","content-type":"application\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/cti2.1144","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,9,6]],"date-time":"2023-09-06T10:51:31Z","timestamp":1693997491000},"score":1,"resource":{"primary":{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/10.1002\/cti2.1144"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2020,1]]},"references-count":68,"journal-issue":{"issue":"6","published-print":{"date-parts":[[2020,1]]}},"alternative-id":["10.1002\/cti2.1144"],"URL":"https:\/\/doi.org\/10.1002\/cti2.1144","archive":["Portico"],"relation":{},"ISSN":["2050-0068","2050-0068"],"issn-type":[{"value":"2050-0068","type":"print"},{"value":"2050-0068","type":"electronic"}],"subject":[],"published":{"date-parts":[[2020,1]]},"assertion":[{"value":"2020-03-06","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2020-05-18","order":1,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2020-06-18","order":2,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}],"article-number":"e1144"}}