MAPK ERK Signaling Regulates the TGF-β1-Dependent Mosquito Response to Plasmodium falciparum
Figure 6
A model of MEK-ERK signaling in TGF-β1-dependent control of P. falciparum development.
Human TGF-β1 ingested during the blood meal activates MEK-ERK signaling in mosquito cells. Activation of ERK inhibits NOS gene expression which reduces nitric oxide synthase levels and the synthesis of reactive oxygen and nitrogen species. MEK-ERK signaling may inhibit the expression of other anti-parasite genes as well that function together with NOS to limit parasite development. Inhibition of the expression of NOS and other anti-parasite gene products would favor P. falciparum development in the mosquito midgut. In contrast, inhibition of MEK-ERK signaling by the MEK inhibitors PD98059 or U0126 increases anti-parasite activity, including TGF-β1-dependent NOS gene expression. Increased NOS expression results in higher nitric oxide synthase enzyme levels and the generation of inflammatory levels of reactive oxygen and nitrogen species [7] that are toxic to the parasite.