Please use this identifier to cite or link to this item: https://hdl.handle.net/10137/5262
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dc.contributor.authorWoodberry Ten
dc.contributor.authorLoughland JRen
dc.contributor.authorMinigo Gen
dc.contributor.authorBurel JGen
dc.contributor.authorAmante FHen
dc.contributor.authorPiera KAen
dc.contributor.authorMcNeil Yen
dc.contributor.authorYeo TWen
dc.contributor.authorGood MFen
dc.contributor.authorDoolan DLen
dc.contributor.authorEngwerda CRen
dc.contributor.authorMcCarthy JSen
dc.contributor.authorAnstey NMen
dc.date2017en
dc.date.accessioned2018-05-15T23:00:34Zen
dc.date.available2018-05-15T23:00:34Zen
dc.date.issued2017en
dc.identifier.citationInfection and immunity 2017; 85(6)en
dc.identifier.urihttps://hdl.handle.net/10137/5262en
dc.description.abstractPlasmodium vivax malaria remains a major public health problem. The requirements for acquisition of protective immunity to the species are not clear. Dendritic cells (DC) are essential for immune cell priming but also perform immune regulatory functions, along with regulatory T cells (Treg). An important function of DC involves activation of the kynurenine pathway via indoleamine 2,3-dioxygenase (IDO). Using a controlled human experimental infection study with blood-stage P. vivax, we characterized plasmacytoid DC (pDC) and myeloid DC (mDC) subset maturation, CD4+ CD25+ CD127lo Treg activation, and IDO activity. Blood samples were collected from six healthy adults preinoculation, at peak parasitemia (day 14; ∼31,400 parasites/ml), and 24 and 48 h after antimalarial treatment. CD1c+ and CD141+ mDC and pDC numbers markedly declined at peak parasitemia, while CD16+ mDC numbers appeared less affected. HLA-DR expression was selectively reduced on CD1c+ mDC, increased on CD16+ mDC, and was unaltered on pDC. Plasma IFN-γ increased significantly and was correlated with an increased kynurenine/tryptophan (KT) ratio, a measure of IDO activity. At peak parasitemia, Treg presented an activated CD4+ CD25+ CD127lo CD45RA- phenotype and upregulated TNFR2 expression. In a mixed-effects model, the KT ratio was positively associated with an increase in activated Treg. Our data demonstrate that a primary P. vivax infection exerts immune modulatory effects by impairing HLA-DR expression on CD1c+ mDC while activating CD16+ mDC. Induction of the kynurenine pathway and increased Treg activation, together with skewed mDC maturation, suggest P. vivax promotes an immunosuppressive environment, likely impairing the development of a protective host immune response.en
dc.language.isoengen
dc.subjectPlasmodium vivaxen
dc.subjectTregen
dc.subjectdendritic cellsen
dc.subjectindoleamine 2,3-dioxygenaseen
dc.titleEarly Immune Regulatory Changes in a Primary Controlled Human Plasmodium vivax Infection: CD1c+ Myeloid Dendritic Cell Maturation Arrest, Induction of the Kynurenine Pathway, and Regulatory T Cell Activation.en
dc.typeJournal Articleen
dc.identifier.journaltitleInfection and immunityen
dc.identifier.doi10.1128/IAI.00986-16en
dc.identifier.pubmedidhttps://www.ezpdhcs.nt.gov.au/login?url=https://www.ncbi.nlm.nih.gov/pubmed//28320838en
dc.subject.meshAdulten
dc.subject.meshBiomarkersen
dc.subject.meshDendritic Cellsen
dc.subject.meshFemaleen
dc.subject.meshHLA-DR Antigensen
dc.subject.meshHealthy Volunteersen
dc.subject.meshHumansen
dc.subject.meshIndoleamine-Pyrrole 2,3,-Dioxygenaseen
dc.subject.meshKynurenineen
dc.subject.meshMalaria, Vivaxen
dc.subject.meshMaleen
dc.subject.meshPlasmodium vivaxen
dc.subject.meshT-Lymphocytes, Regulatoryen
dc.subject.meshTryptophanen
dc.subject.meshUp-Regulationen
dc.subject.meshYoung Adulten
dc.subject.meshLymphocyte Activationen
dc.identifier.affiliationGlobal and Tropical Health Division, Menzies School of Health Research and Charles Darwin University, Darwin, NT, Australia..en
dc.identifier.affiliationGlobal and Tropical Health Division, Menzies School of Health Research and Charles Darwin University, Darwin, NT, Australia jessica.loughland@menzies.edu.au..en
dc.identifier.affiliationGlobal and Tropical Health Division, Menzies School of Health Research and Charles Darwin University, Darwin, NT, Australia..en
dc.identifier.affiliationQIMR Berghofer Institute of Medical Research, Brisbane, Queensland, Australia..en
dc.identifier.affiliationQIMR Berghofer Institute of Medical Research, Brisbane, Queensland, Australia..en
dc.identifier.affiliationGlobal and Tropical Health Division, Menzies School of Health Research and Charles Darwin University, Darwin, NT, Australia..en
dc.identifier.affiliationGlobal and Tropical Health Division, Menzies School of Health Research and Charles Darwin University, Darwin, NT, Australia..en
dc.identifier.affiliationGlobal and Tropical Health Division, Menzies School of Health Research and Charles Darwin University, Darwin, NT, Australia.. Lee Kong Chian School of Medicine, Nanyang Technological University, Singapore.. Communicable Disease Centre, Institute of Infectious Diseases and Epidemiology, Tan Tock Seng Hospital, Singapore..en
dc.identifier.affiliationGlycomics Institute, Griffith University, Queensland, Australia..en
dc.identifier.affiliationQIMR Berghofer Institute of Medical Research, Brisbane, Queensland, Australia.. Australian Institute of Tropical Health and Medicine, James Cook University, Cairns, Australia..en
dc.identifier.affiliationQIMR Berghofer Institute of Medical Research, Brisbane, Queensland, Australia..en
dc.identifier.affiliationQIMR Berghofer Institute of Medical Research, Brisbane, Queensland, Australia..en
dc.identifier.affiliationGlobal and Tropical Health Division, Menzies School of Health Research and Charles Darwin University, Darwin, NT, Australia.. Royal Darwin Hospital, Darwin, Australia..en
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