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dc.contributor.authorJ. Robinson, Leanneen_US
dc.contributor.authorC. D⿿Ombrain, Martheen_US
dc.contributor.authorI.Stanisic, Danielleen_US
dc.contributor.authorTaraika, Jacken_US
dc.contributor.authorBernard, Nicholasen_US
dc.contributor.authorS. Richards, Jacken_US
dc.contributor.authorG. Beeson, Jamesen_US
dc.contributor.authorTavul, Livingstoneen_US
dc.contributor.authorMichon, Pascalen_US
dc.contributor.authorMueller, Ivoen_US
dc.contributor.authorSchofield, Louisen_US
dc.description.abstractThe role of early to intermediate Plasmodium falciparum-induced cellular responses in the development of clinical immunity to malaria is not well understood, and such responses have been proposed to contribute to both immunity and risk of clinical malaria episodes. To investigate whether P. falciparum-induced cellular responses are able to function as predictive correlates of parasitological and clinical outcomes, we conducted a prospective cohort study of children (5 to 14 years of age) residing in a region of Papua New Guinea where malaria is endemic Live, intact P. falciparum-infected red blood cells were applied to isolated peripheral blood mononuclear cells obtained at baseline. Cellular cytokine production, including production of interleukin-2 (IL-2), IL-4, IL-6, IL-10, tumor necrosis factor (TNF) (formerly tumor necrosis factor alpha), and gamma interferon (IFN- ), was measured, and the cellular source of key cytokines was investigated. Multicytokine models revealed that increasing P. falciparum-induced IL-6 production was associated with an increased incidence of P. falciparum clinical episodes (incidence rate ratio [IRR], 1.75; 95% confidence interval [CI], 1.20 to 2.53), while increasing P. falciparum-induced TNF and IFN- production was associated with a reduced incidence of clinical episodes (IRR for TNF, 0.55 [95% CI, 0.38 to 0.80]; IRR for IFN- , 0.71 [95% CI, 0.55 to 0.90]). Furthermore, we found that monocytes/macrophages and -T cells are important for the P. falciparuminduced production of IL-6 and TNF. Early to intermediate cellular cytokine responses to P. falciparum may therefore be important correlates of immunity and risk of symptomatic malaria episodes and thus warrant detailed investigation in relation to the development and implementation of effective vaccines.en_US
dc.publisherAmerican Society for Microbiologyen_US
dc.publisher.placeUnited Statesen_US
dc.relation.ispartofjournalInfection and Immunityen_US
dc.subject.fieldofresearchCellular Immunologyen_US
dc.titleCellular Tumor Necrosis Factor, Gamma Interferon, and Interleukin-6 Responses as Correlates of Immunity and Risk of Clinical Plasmodium falciparum Malaria in Children from Papua New Guineaen_US
dc.typeJournal articleen_US
dc.type.descriptionC1 - Peer Reviewed (HERDC)en_US
dc.type.codeC - Journal Articlesen_US
gro.hasfulltextNo Full Text

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