Abstract:
Erythrocytic mechanisms involved in malarial infection are poorly understood. We have found that signaling via the erythrocyte ß2-adrenergic receptor and heterotrimeric guanine nucleotide–binding protein (Gs) regulated the entry of the human malaria parasite Plasmodium falciparum. Agonists that stimulate cyclic adenosine 3',5'-monophosphate production led to an increase in malarial infection that could be blocked by specific receptor antagonists. Moreover, peptides designed to inhibit Gs protein function reduced parasitemia in P. falciparum cultures in vitro, and ß-antagonists reduced parasitemia of P. berghei infections in an in vivo mouse model. Thus, signaling via the erythrocyte ß2-adrenergic receptor and Gs may regulate malarial infection across parasite species.
Image depicts the cross sectional views through 3D reconstructions of signaling in human erythrocytes in the absence or presence of infection by the malaria parasite Plasmodium falciparum . Distribution of host signaling heterotimeric Gs protein is in green and parasite is in blue.
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