Abstract
SummaryMalaria in malaria‐naïve adults is associated with an inflammatory response characterized by expression of specific activation markers on innate immune cells. Here, we investigate activation and adhesion marker expression, and cytokine production in monocytes from children presenting with cerebral malaria (CM, n = 36), severe malarial anaemia (SMA, n = 42) or uncomplicated malaria (UM, n = 66), and healthy aparasitemic children (n = 52) in Blantyre, Malawi. In all malaria groups, but particularly in the two severe malaria groups, monocyte expression of CD11b, CD11c, CD18, HLA‐DR and CD86, and percentages of TNF‐α‐ and IL‐6‐producing monocytes were lower than in healthy controls, while expression of CD11a, TLR2 and TLR4 was lower in children with severe malaria compared with controls. These levels mostly normalized during convalescence, but percentages of cytokine‐producing monocytes remained suppressed in children with SMA. In all malaria groups, especially the SMA group, a greater proportion of monocytes were loaded with haemozoin than among controls. In a P. falciparum hyperendemic area, monocytes in children with acute symptomatic malaria have reduced expression of adhesion molecules and activation markers and reduced inflammatory cytokine production. This immune suppression could be due to accumulation of haemozoin and/or previous exposure to P. falciparum.
Highlights
The acquisition of protective immunity against malaria requires repeated infections over a number of years [1]
Clinical malaria is characterized by low expression of integrins on monocytes During acute malaria, the mean expression levels of integrins CD11a, CD11b, CD11c and CD18 were significantly lower than in controls for each clinical form of malaria, with the exception of CD11a in UM (Fig. 2a–d)
Clinical malaria is characterized by low expression of Toll-like receptors (TLRs), HLA-DR and CD86 on monocytes
Summary
The acquisition of protective immunity against malaria requires repeated infections over a number of years [1]. Monocytes are precursors of macrophages and dendritic cells. Their main functions are phagocytosis, antigen presentation and cytokine production [3]. Proinflammatory cytokines, such as TNF-a and IL-6 which are produced by monocytes among other cells, are elevated in severe malaria and appear to be important for controlling infection [4]. Their excessive production has been linked to immunopathogenesis in malaria [5, 6]
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