Further, within the transmembrane receptor category of upstream regulators, Toll-Like Receptors 4 (TLR4), a pathogen recognition receptor that can bind to GPI anchors derived from the malaria parasite43, was activated in adults and inhibited in children (Fig. 3h), consistent with an increased ability of monocytes from adults to bind parasite products and induce inflammation. Here, TLR4 is linked to malaria.