Our laboratory’s previous microarray analysis of subjects with Plasmodium falciparum revealed up-regulation of Toll-like receptor, NF-kB, TNF-α, IFN-γ, IL-1β, p38 MAPK, and MHC molecules. We performed further time-course microarray analysis focusing on malaria pathogenesis by using peripheral leukocytes as a cellular model. We found up-regulation of coagulation-related genes (SERPINB2, thrombomodulin, thrombospondin), heat shock proteins, glycolytic enzymes, glucose transporters, and vacuolar H+-ATPases in acute febrile malaria. In early malaria, prior to detectable parasitemia, CD36 and ICAM1 were up-regulated. During acute malaria, a correlation was observed between IL-1ß and heat shock proteins, suggesting heat shock protein response may be in the febrile response induced by IL-1ß. CD163, a hemoglobin scavenger receptor, was up-regulated in acute malaria to potentially facilitate free hemoglobin up-take by peripheral leukocytes. In acute malaria, high MafB gene expression was negatively correlated with down-regulation of hemoglobin and platelet counts. Consistent with a down-regulation of hemoglobin expression, peripheral RBC counts tended to increase during the acute malaria. In our model, up-regulations of RBC and/or leucocyte binding mediators like CD36, ICAM1, thrombospondin, and thrombomodulin may contribute to the pathogenesis of cerebral malaria. Similarly, up-regulation of genes coding for glycolytic enzymes, glucose transporter and H+-ATPases may contribute to the hypoglycemia and metabolic acidosis frequently observed in seriously ill malaria patients. Overall gender effects on gene expression profiles between male and female subjects were not apparent, except that some hemoglobins were significantly down-regulated in male versus female; suggesting males may be more prone to the development of malaria associate anemia
