Plasmodium falciparum—the species that causes the most virulent human form of malaria—infects both hepatocytes and mature red blood cells (erythrocytes). The erythrocytic stages are responsible for the symptoms associated with the disease (e.g., fever, headache, and back pain), but the mechanisms involved in malarial infection have been poorly understood. In the September 19 Science, Travis Harrison and colleagues at the Feinberg School of Medicine show that signaling via the erythrocyte β2-adrenergic receptor and Gαs regulates erythrocytic stages of malarial infection across Plasmodium species (Science, 301:1734-1736, September 19, 2003).

Harrison et al. examined cocultures of parasites and erythrocytic peptides and observed that agonists that stimulate cyclic adenosine 3',5'-monophosphate production caused an increase in malarial infection that could be blocked by specific receptor antagonists. In addition, the authors showed that peptides designed to inhibit Gαs protein function reduced parasitemia in P. falciparum cultures in vitro, and β-antagonists reduced parasitemia of P. berghei infections in an in vivo murine model.

"Although the physiological functions of G protein receptors and their associated signaling mechanisms in erythrocytes are not well understood, an emerging idea is that they may contribute to interactions with endothelial cells. Because both Gαs and β2-AR were internalized and associated with the vacuolar parasite, their activation in malarial infection may regulate a step of vacuole formation that is conserved across parasite species," conclude the authors.