Changes in monocyte subsets are associated with clinical outcomes in severe malarial anaemia and cerebral malaria

Abstract

Monocytes are plastic heterogeneous immune cells involved in host-parasite interactions critical for malaria pathogenesis. Human monocytes have been subdivided into three populations based on surface expression of CD14 and CD16. We hypothesised that proportions and phenotypes of circulating monocyte subsets can be markers of severity or fatality in children with malaria. To address this question, we compared monocytes sampled in children with uncomplicated malaria, severe malarial anaemia, or cerebral malaria. Flow cytometry was used to distinguish and phenotype monocyte subsets through CD14, CD16, CD36 and TLR2 expression. Data were first analysed by univariate analysis to evaluate their link to severity and death. Second, multinomial logistic regression was used to measure the specific effect of monocyte proportions and phenotypes on severity and death, after adjustments for other variables unrelated to monocytes. Multivariate analysis demonstrated that decreased percentages of non-classical monocytes were associated with death, suggesting that this monocyte subset has a role in resolving malaria. Using univariate analysis, we also showed that the role of non-classical monocytes involves a mostly anti-inflammatory profile and the expression of CD16. Further studies are needed to decipher the functions of this sub-population during severe malaria episodes, and understand the underlying mechanisms.

Comparison of leucocyte profiles between healthy children and those with asymptomatic and symptomatic Plasmodium falciparum infections

“…Nonetheless, a positive correlation was observed between parasite densities and both the absolute numbers and the proportions of CD14 + monocytes in the asymptomatic group. Further work is needed to characterize different subtypes (classical, intermediate and nonclassical) of monocytes, since changes in the numbers of these have been implicated in infection outcomes with P. falciparum infection [55].…”

Management of cell death in parasitic infections

“…During this process, CD36 clustering leads to activation of both ERK and p38MAPK signaling cascades [72]. Consistent with this, CD14 + CD16and CD14 + CD16 hi blood monocytes from children with acute malaria show impaired expression of CD36 and reduced phagocytic capacity in vitro compared to samples isolated from children six weeks after recovery [77], therefore suggesting that lower CD36 expression by two population of monocytes (CD14 + CD16 − and CD14 + CD16 + ) is related to severity of the infection and consequent death [78]. These data are strongly supported by the fact that African populations contain an exceptionally high frequency of mutations in CD36, which, by causing CD36 deficiency, are associated with susceptibility to severe malaria [79].…”

Longitudinal immune profiling after radiation-attenuated sporozoite vaccination reveals coordinated immune processes correlated with malaria protection

“…Specifically, protection-associated interferon transcriptional responses were correlated with increased levels of both CD14+ and NC monocyte subsets, while the non-protective interferon responses after the 1 st immunization were correlated with CD14+ subsets only. Interestingly, increased abundance of non-classical CD14dim CD16+ monocytes has been previously linked to reduced serum inflammatory cytokine levels and less severe malaria in children [59], pointing to a key role for these monocyte subsets in resolving the inflammatory response to malaria. Thus, NC monocytes may play an immune regulatory role in response to RAS immunization, and effective vaccine mediated immunity may require a balance between classical and non-classical monocyte responses.…”