TNF and malaria: Finally, since high concentrations of TNF-α have been reported to impair Treg activity (by upregulating and then signaling via TNFR2, leading to decreased FOXP3 mRNA and protein expression [46]), and the functional impairment of Tregs observed in rheumatoid arthritis patients can be reversed by anti-TNF-α antibodies [47], we considered the hypothesis that the high levels of TNF-α seen in severe malaria patients [13],[15], might upregulate TNFR2 and impair Treg function.