Four TLR9 single nucleotide polymorphisms (SNPs) namely: rs187084 (C-1486 T), rs5743836(C-1237 T), rs352139 (G + 1174A) and rs352140 (G + 2848A) were genotyped by direct sequencing, and their attributable and relative risks for symptomatic malaria determined.
TLR9T1237C rs5743836CC was associated with an increased risk of developing malaria (p=0.03), although it was found with the same frequency in uncomplicated and severe malaria cases.
Taken together, these results corroborated the involvement of TLR9 in CM pathogenesis and suggest that interference with the activation of this receptor is a promising strategy to prevent deleterious inflammatory response mediating pathogenesis and severity of malaria.
Although Toll-like receptor 9 (TLR9) has been implicated in cytokine and type I interferon (IFN) production during malaria in humans and mice, the high AT content of the Plasmodium falciparum genome prompted us to examine the possibility that malarial DNA triggered TLR9-independent pathways.
No convincing association was found with polymorphisms in TLR9 for malaria severity, in either Gambian or Malawian populations, using both case-control and family based study designs.
Patients with severe and mild malaria showed increased surface expression of TLR2 and TLR4 on CD14(+)monocytes and myeloid dendritic cells (MDCs) and decreased intracellular expression of TLR9 on plasmacytoid dendritic cells (PDCs), compared to those of healthy controls.