Cellular 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 Guinea

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Title Cellular 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 Guinea
Author Robinson, Leanne J.; D'Ombrain, Marthe C.; Stanisic, Danielle; Taraika, Jack; Bernard, Nicholas; Richards, Jack S.; Beeson, James G.; Tavul, Livingstone; Michon, Pascal; Mueller, Ivo; Schofield, Louis
Journal Name Infection and Immunity
Year Published 2009
Place of publication United States
Publisher American Society for Microbiology
Abstract The 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.
Peer Reviewed Yes
Published Yes
Alternative URI http://dx.doi.org/10.1128/IAI.00211-09
Volume 77
Issue Number 7
Page from 3033
Page to 3043
ISSN 0019-9567
Date Accessioned 2011-03-22
Date Available 2011-04-14T07:00:47Z
Language en_AU
Research Centre Institute for Glycomics
Faculty Faculty of Science, Environment, Engineering and Technology
Subject Cellular Immunology
URI http://hdl.handle.net/10072/38168
Publication Type Journal Articles (Refereed Article)
Publication Type Code c1x

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