Abstract:
Plasmodium falciparum malaria is one of the leading causes of childhood morbidity and mortality in sub-Saharan Africa. The host immune response to P. falciparum is a critical determinant of malarial pathogenesis and disease outcomes. Macrophage migration inhibitory factor (MIF) is a central regulator of innate immune responses to bacterial and parasitic infections. Our recent investigations demonstrated that peripheral blood MIF production was suppressed in children with severe malaria. Because examination of MIF production in children with active disease does not account for the inherent ability of the host to generate MIF, basal circulating MIF and peripheral blood mononuclear cell (PBMC) MIF transcript levels were determined in healthy children with a history of either mild or severe malaria. Children with prior mild malaria had higher plasma MIF levels and PBMC MIF transcripts than children with an identical number of previous episodes of severe malaria. These results suggest that increased basal MIF production may be important in generating immune responses that protect against the development of severe malaria.