Monocyte activation and cytokine production in Malawian children presenting with P. falciparum malaria

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.

Cytokine Profiles in Malawian Children Presenting with Uncomplicated Malaria, Severe Malarial Anemia, and Cerebral Malaria

“…Interestingly, there are some apparent paradoxes between the cytokine concentrations reported in this paper and the monocyte intracellular cytokine staining (42) and immunophenotyping (6) findings that we have reported previously for the same study participants. We observed decreased IL-6 and TNF-α production by monocytes in children with different forms of malaria (42).…”

“…We observed decreased IL-6 and TNF-α production by monocytes in children with different forms of malaria (42). This indicates that the elevated levels of these cytokines in serum in the current report are produced by cells other than monocytes (or macrophages), most likely T cells and NK cells.…”

“…Although we have reported on the proportion of cytokine-producing monocytes from each of these three malaria groups (42), inclusion of an intracellular cytokine analysis for other cytokine-producing cells could enable the identification of the main producers of the cytokines present in the corresponding serum/plasma. Lastly, although this study analyzed serum samples for concentrations of some cytokines, analysis of additional cytokines that are suspected to play some roles in malaria immunity (40, 41) as well as concentrations of chemokines such as RANTES and IP-10, which have been shown to vary with malaria severity (40), would provide additional insight into their separate and/or synergistic roles in malaria.…”

T cell subtypes and reciprocal inflammatory mediator expression differentiate P. falciparum memory recall responses in asymptomatic and symptomatic malaria patients in southeastern Haiti

“…The cause of this down regulation could not be ascertained, and it remains to be determined if this cellular phenotype is the result of an unknown immuno-modulatory process of the host or from a parasite-derived factor. It is worth noting that this same phenomenon of decreased HLA-DR expression was recently observed in monocytes obtained from Malawian children presenting at hospital with malaria [64], suggesting that this process may affect all leukocytes. Further research is certainly needed before any further inferences could be drawn.…”

“…Later it was shown that this immunological phenomenon required cooperation between antibodies and monocytes in order to be effective [41, 82, 83]. Patient data from Malawi has recently demonstrated that in patients with severe malaria, monocytes have decreased expression of activation markers compared to those from patients with uncomplicated malaria, underscoring the role that activated monocytes play in controlling morbidity [64]. …”