Gene expression profiling of monocyte in response to Pf-iRBC stimulation from Pf-PCR negative Malian children and adults during dry season.
In malaria-naïve individuals, P. falciparum (Pf) infection results in numerous Pf-infected red blood cells (iRBCs) that trigger systemic inflammation and fever. Conversely, repeatedly infected individuals in endemic areas are often asymptomatic and have low levels of iRBCs, even children who have yet to acquire reliably protective antibodies. The molecular mechanisms underlying these clinical observations are unclear. PBMCs collected from Malian children before the malaria season responded to iRBCs by producing pyrogenic, pro-inflammatory mediators such as IL-1ß, IL-6 and TNF. However, following febrile malaria there was a marked shift in the response to iRBCs with the same children's PBMCs producing lower levels of those cytokines. These data suggest that malaria-induced epigenetic reprogramming of innate immune cells may play a role in immunity to malaria. Accordingly, age-stratified analysis of monocytes collected before the malaria season showed an inverse relationship between age and pro-inflammatory cytokine production capacity. Overall design: Total 24 monocytes samples were analyzed. Eight monocyte samples from Pf-iRBC stimulated Malian Children were compared with eight monocyte from Pf-iRBC stimulated Malian adults. Four unstimulated monocyte samples from Malian children and four from Malian adults were used as internal control, these unstimulated samples were independent of Pf-iRBC stimulated experimental monocyte sample.