Abstract
The study explored the role of differential RANTES concentrations, its receptor CCR5 expression and resulting immunomodulation in the pathogenesis and/or recovery from falciparum malaria. The study population included cases of uncomplicated malaria (UC-M, N=128, enrolled on follow-up basis), severe malaria (SM, N=25), and healthy controls (N=112). Serum RANTES and TNF-α levels were evaluated by ELISA. Monocyte levels and activation profile were studied by flow cytometry. Differential mRNA expression profile was studied by real-time PCR. Blood parasite count was evaluated by registered pathologists. RANTES concentration was significantly downregulated in SM cases compared to UC-M (P=.046) and controls (P<.001). Expression of monocyte marker mCD14, activation markers CCR5 and CD40, and downstream effector cytokine TNF-α was significantly higher in malaria cases compared to controls, in SM cases compared to UC-M. TNF-α expression correlated positively with CD40 and CCR5 expressions. Follow-up-based analysis showed that RANTES concentrations increased on recovery compared to baseline in UC-M cases (P=.106) and inversely correlated with malaria parasite load, mCD14, CCR5 and CD40, and TNF-α expressions. These findings suggest an important association of RANTES concentrations in Plasmodium falciparum malaria disease pathogenesis, as well as recovery, mediated through differential modulation and regulated activation of monocytes and cytokine TNF-α.