Robinson, Leanne J., D'Ombrain, Marthe C., Stanisic, Danielle I., Taraika, Jack, Bernard, Nicholas, Richards, Jack S., Beeson, James G., Tavul, Livingstone, Michon, Pascal, Mueller, Ivo, and Schofield, Louis (2009) 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. Infection and Immunity, 77 (7). pp. 3033-3043.

PDF (Published Version) - Published Version Restricted to Repository staff only

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-γ), 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-γ 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-γ, 0.71 [95% CI, 0.55 to 0.90]). Furthermore, we found that monocytes/macrophages and γδ-T cells are important for the P. falciparum-induced 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.

Item ID:	35866
Item Type:	Article (Research - C1)
ISSN:	1098-5522
Funders:	National Health and Medical Research Council (NHMRC)
Projects and Grants:	NHMRC Grant No. 516735, NHMRC Grant No. 406601
Date Deposited:	31 Oct 2014 01:23
FoR Codes:	11 MEDICAL AND HEALTH SCIENCES > 1103 Clinical Sciences > 110309 Infectious Diseases @ 50% 11 MEDICAL AND HEALTH SCIENCES > 1107 Immunology > 110799 Immunology not elsewhere classified @ 50%
SEO Codes:	97 EXPANDING KNOWLEDGE > 970111 Expanding Knowledge in the Medical and Health Sciences @ 100%
Downloads:	Total: 5
	More Statistics