Increased eosinophil activity in acutePlasmodium falciparuminfection—association with cerebral malaria

Abstract

To assess the eosinophil response to Plasmodium falciparum infection a cohort of initially parasite-free Ghanaian children was followed for 3 months. Seven of nine children who acquired an asymptomatic P. falciparum infection showed increase in eosinophil counts, while a decrease was found in seven of nine children with symptomatic malaria, and no change was observed in 14 children who remained parasite-free. In a hospital-based study, paediatric patients with cerebral malaria (CM), severe anaemia (SA), or uncomplicated malaria (UM) had uniformly low eosinophil counts during the acute illness followed by eosinophilia 30 days after cure. Plasma levels of eosinophil cationic protein (ECP) and eosinophil protein X (EPX) were measured as indicators of eosinophil activation. In spite of the low eosinophil counts, ECP levels were increased on day 0 and significantly higher in patients with CM (geometric mean (95% confidence interval) 8.5 ng/ml (6.8-10.7 ng/ml)) than in SA (4.7 ng/ml (3.0-7.5 ng/ml)) and UM patients (4.3 ng/ml (3.6-5.3 ng/ml), P < 0.001). A similar pattern was found for EPX. It thus appears that the low eosinophil counts may be due to tissue sequestration and destruction rather than decreased production. The plasma levels of the granule proteins correlated with levels of tumour necrosis factor and soluble IL-2 receptor, implicating inflammatory responses and T cell activation as causes of the eosinophil activation. By contrast, the eosinophil induction did not appear to be part of a Th2-like response. Eosinophil granule proteins may be important in both control of malaria infection and the pathogenesis of severe malaria.

The Transcription Factor T-bet Regulates Parasitemia and Promotes Pathogenesis duringPlasmodium bergheiANKA Murine Malaria

“…Eotaxin is well recognized as a potent chemoattractant for eosinophils (46,47). Although eosinophil accumulation was not compared in WT versus Tbx21 2/2 mice, it has previously been reported that Ghanian pediatric patients with CM had uniformly low eosinophil counts because of tissue sequestration and destruction rather than decreased production during acute illness followed by eosinophilia 30 d after cure (48). Importantly, the eotaxin receptor is expressed by Th2 CD4 + T cells, and eotaxin is critical for the generation and maintenance of Th2 cells at allergenic sites and promotes the production of IL-4 and IL-5 (49,50).…”

Identification of Inflammatory Biomarkers for Pediatric Malarial Anemia Severity Using Novel Statistical Methods

“…In addition, eotaxin is a strong chemoattractant for (42), which are also associated with allergic reactions (44). However, eosinophil responses have been reported during malaria infections (25) and are important for producing functional IL-13 (44). Since eosinophil responses are associated with hematological recovery following malarial treatment (8) and Hb levels typically decrease following successful parasite clearance with antimalarial drugs (7), it is tempting to postulate that the IL-13/eotaxin pathway may negatively regulate Hb levels during a malaria infection through eosinophilic responses.…”

“…Since eosinophil responses are associated with hematological recovery following malarial treatment (8) and Hb levels typically decrease following successful parasite clearance with antimalarial drugs (7), it is tempting to postulate that the IL-13/eotaxin pathway may negatively regulate Hb levels during a malaria infection through eosinophilic responses. Kurtzhals et al (25) observed that during acute infection, eosinophils were sequestered in deep tissues, while recent studies showed that the production of high levels of IL-13 in malaria-infected children was associated with hepatomegaly (52). Eosinophils are known to produce granule proteins (e.g., eosinophil cationic protein [ECP]) whose levels are correlated with TNF-␣ and IL-2R during malarial infections (25).…”

“…Kurtzhals et al (25) observed that during acute infection, eosinophils were sequestered in deep tissues, while recent studies showed that the production of high levels of IL-13 in malaria-infected children was associated with hepatomegaly (52). Eosinophils are known to produce granule proteins (e.g., eosinophil cationic protein [ECP]) whose levels are correlated with TNF-␣ and IL-2R during malarial infections (25). Findings presented here showing that soluble IL-2R levels are significant negative predictors of Hb levels are consistent with previous studies showing that elevated IL-2R is associated with enhanced malaria disease severity (18).…”

Human Genetic Contribution to the Outcome of Infection with Malaria Parasites

“…In addition, there is suggestion that histamine might influence the polarization of T-helper cell development through inhibitory effects on dendritic cells (Idzko et al, 2002). Reports indicate that specific components of the innate immune system, including eosinophils (Kurtzhals et al, 1998), basophils (Nyakeriga et al, 2003), and Mast cells (MCs) (Furuta et al, 2006), could play important roles in the pathogenesis of malaria. Increased levels of histamine in plasma and tissue, derived from basophils and MCs, notably following stimulation by IgE through the high affinity receptor FcεR1, are associated with the severity of disease in humans infected with P. falciparum and in animal malaria models (Bhattacharya et al, 1988;Srichaikul et al, 1976).…”