Young children are at greatest risk for malaria-associated morbidity and mortality. The immune response of young children differs in fundamental ways from that of adults, and these differences likely contribute to the increased susceptibility of children to severe malaria and to their delayed development of immunity. Elevated levels of pro-inflammatory cytokines and chemokines in the peripheral blood during acute infection contribute to the control of parasitaemia, but are also responsible for much of the immunopathology seen during symptomatic disease. Clinical immunity to malaria may depend upon the ability to regulate these pro-inflammatory responses, possibly through mechanisms of immunologic tolerance. In order to explore the effect of age on the immune response to malaria and the development of clinical immunity, cytokines and chemokines were measured in the plasma of children at day 0 of an acute malaria episode and during convalescence.
Younger children presenting with acute malaria exhibited much higher levels of TNF, IL2, and IL6, as well as increased Th1 associated chemokines IP10, MIG, and MCP1, compared to older children with acute malaria. Additionally, the regulatory cytokines IL10 and TNFRI were dramatically elevated in younger children compared to older children during acute infection, indicating that regulatory as well as pro-inflammatory cytokine responses are dampened in later childhood.
Together these data suggest that there is a profound blunting of the cytokine and chemokine response to malaria among older children residing in endemic settings, which may be due to repeated malaria exposure, intrinsic age-based differences in the immune response, or both.
WHO. World malaria report 2016. Geneva: World Health Organization; 2016.
Kaminuma O, Kitamura F, Miyatake S, Yamaoka K, Miyoshi H, Inokuma S, et al. T-box 21 transcription factor is responsible for distorted T(H)2 differentiation in human peripheral CD4+ T cells. J Allergy Clin Immunol. 2009;123(813–23):e3.
Mshana RN, Boulandi J, Mshana NM, Mayombo J, Mendome G. Cytokines in the pathogenesis of malaria: levels of IL-I beta, IL-4, IL-6, TNF-alpha and IFN-gamma in plasma of healthy individuals and malaria patients in a holoendemic area. J Clin Lab Immunol. 1991;34:131–9. PubMed
Robinson LJ, D’Ombrain MC, Stanisic DI, Taraika J, Bernard N, Richards JS, et al. 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. Infect Immun. 2009;77:3033–43. CrossRefPubMedPubMedCentral
Ateba-Ngoa U, Adegnika AA, Zinsou JF, Kassa Kassa RF, Smits H, Massinga-Loembe M, et al. Cytokine and chemokine profile of the innate and adaptive immune response of Schistosoma haematobium and Plasmodium falciparum single and co-infected school-aged children from an endemic area of Lambaréné, Gabon. Malar J. 2015;14:94. CrossRefPubMedPubMedCentral
Farrington L, Vance H, Rek J, Prahl P, Jagannathan P, Katureebe A, Arinaitwe E, Kamya MR, Dorsey G, Feeney M. Both inflammatory and regulatory cytokine responses to malaria are blunted with increasing age in highly exposed children data sets. Figshare, 2017. http://dx.doi.org/10.6084/m9.figshare.5518825.
- Both inflammatory and regulatory cytokine responses to malaria are blunted with increasing age in highly exposed children
Moses R. Kamya
Margaret E. Feeney
- BioMed Central
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