Kinetics of chemokine receptor modulation induced by synthetic hemozoin in immature dendritic cells.

We have previously investigated the migratory properties of dendritic cells (DC) during malaria infection. DC are specialized in initiating T-cell responses and DC trafficking is integral to their function. The migratory pattern of DC is defined by the surface -chemokine receptor (CCR) expression. As immature cells, DC express inflammatory CCR and patrol peripheral tissues. Upon encountering antigen, a maturation process is initiated with upregulation of lymphoid CCR. This enables mature DC to migrate to the lymph nodes where they encounter naïve T-cells and activate them. Our previous results indicated that synthetic hemozoin (sHZ) might induce a partial maturation of DC, including an upregulation of the expression of lymphoid CCR. In order to evaluate the kinetics of CCR modulation, we analyzed the phenotype of DC at different time points upon stimulation with sHZ. Our results indicate that upregulation of CCR is notable already after 12 hours post stimulation and is essentially maintained after 60 hours of culture, thus strengthening our previous findings. We hypothesize that sHZ-induced partial maturation of DC might cause insufficient activation of T-cells, thus leading to a state of anergy that may in turn account for the impaired immune responses seen in malaria patients. Therefore, our next step will be to evaluate the proliferative responses of T-cells upon activation of DC exposed to sHZ or other malaria-derived products.