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dc.contributor.authorLoughland, Jessica R
dc.contributor.authorWoodberry, Tonia
dc.contributor.authorField, Matt
dc.contributor.authorAndrew, Dean W
dc.contributor.authorSheelaNair, Arya
dc.contributor.authorDooley, Nicholas L
dc.contributor.authorPiera, Kim A
dc.contributor.authorAmante, Fiona H
dc.contributor.authorKenangalem, Enny
dc.contributor.authorPrice, Ric N
dc.contributor.authorEngwerda, Christian R
dc.contributor.authorAnstey, Nicholas M
dc.contributor.authorMcCarthy, James S
dc.contributor.authorBoyle, Michelle J
dc.contributor.authorMinigo, Gabriela
dc.date.accessioned2020-07-10T04:43:16Z
dc.date.available2020-07-10T04:43:16Z
dc.date.issued2020
dc.identifier.issn2050-0068
dc.identifier.doi10.1002/cti2.1144
dc.identifier.urihttp://hdl.handle.net/10072/395330
dc.description.abstractObjectives: Malaria, caused by Plasmodium infection, remains a major global health problem. Monocytes are integral to the immune response, yet their transcriptional and functional responses in primary Plasmodium falciparum infection and in clinical malaria are poorly understood. Methods: The transcriptional and functional profiles of monocytes were examined in controlled human malaria infection with P. falciparum 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-infection or at convalescence in acute malaria. Results: 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-mediated signalling. Monocytes increased TNF and IL-12 production upon in vitro toll-like receptor stimulation and increased IL-10 production upon in vitro parasite restimulation. Longitudinal phenotypic analyses revealed sustained significant changes in the composition of monocytes following infection, with increased CD14+CD16- and decreased CD14-CD16+ subsets. In acute malaria, monocyte CD64/FcγRI expression was significantly increased in children and adults, while HLA-DR 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. Conclusions: 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.
dc.description.peerreviewedYes
dc.languageEnglish
dc.language.isoeng
dc.publisherWiley
dc.relation.ispartofpagefrome1144:1
dc.relation.ispartofpagetoe1144:18
dc.relation.ispartofissue6
dc.relation.ispartofjournalClinical & Translational Immunology
dc.relation.ispartofvolume9
dc.subject.fieldofresearchBiological sciences
dc.subject.fieldofresearchImmunology
dc.subject.fieldofresearchPharmacology and pharmaceutical sciences
dc.subject.fieldofresearchcode31
dc.subject.fieldofresearchcode3204
dc.subject.fieldofresearchcode3214
dc.subject.keywordsCHMI
dc.subject.keywordsPlasmodium falciparum
dc.subject.keywordsRNA sequencing
dc.subject.keywordsinterferon
dc.subject.keywordsmalaria
dc.titleTranscriptional profiling and immunophenotyping show sustained activation of blood monocytes in subpatent Plasmodium falciparum infection
dc.typeJournal article
dc.type.descriptionC1 - Articles
dcterms.bibliographicCitationLoughland, JR; Woodberry, T; Field, M; Andrew, DW; SheelaNair, A; Dooley, NL; Piera, KA; Amante, FH; Kenangalem, E; Price, RN; Engwerda, CR; Anstey, NM; McCarthy, JS; Boyle, MJ; Minigo, G, Transcriptional profiling and immunophenotyping show sustained activation of blood monocytes in subpatent Plasmodium falciparum infection, Clinical & Translational Immunology, 2020, 9 (6), pp. e1144:1-e1144:18
dcterms.dateAccepted2020-05-18
dcterms.licensehttps://creativecommons.org/licenses/by/4.0/
dc.date.updated2020-07-10T04:33:26Z
dc.description.versionVersion of Record (VoR)
gro.rights.copyright© 2020 The Authors. Clinical & Translational Immunology published by John Wiley & Sons Australia, Ltd on behalf of Australian and New Zealand Society for Immunology, Inc. This is an open access article under the terms of the Creative Commons Attribution License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited.
gro.hasfulltextFull Text
gro.griffith.authorEngwerda, Christian R.
gro.griffith.authorBoyle, Michelle


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