Vacuolar uptake of host components, and a role for cholesterol and sphingomyelin in malarial infection

Erythrocytes, which are incapable of endocytosis or phagocytosis, can be in fected by the malaria parasite Plasmodium falciparum. We find that a transm embrane protein (Duffy), glycosylphosphatidylinositol (GPI)-anchored and cy toplasmic proteins, associated with detergent-resistant membranes (DRMs) th at are characteristic of microdomains in host cell membranes, are internali zed by vacuolar parasites, while the major integral membrane and cytoskelet al proteins are not. The internalized host proteins and a plasmodial transm embrane resident parasitophorous vacuolar membrane (PVM) protein are detect ed in DRMs associated with vacuolar parasites. This is the first report of a host transmembrane protein being recruited into an apicomplexan vacuole a nd of the presence of vacuolar DRMs; it establishes that integral associati on does not preclude protein internalization into the P.falciparum vacuole. Rather, as shown for Duffy, intracellular accumulation occurs at the same rate as that seen for a DRM-associated GPI-anchored protein. Furthermore, n ovel mechanisms regulated by the DRM lipids, sphingomyelin and cholesterol, mediate (i) the uptake of host DRM proteins and (ii) maintenance of the in tracellular vacuole in the non-endocytic red cell, which may have implicati ons for intracellular parasitism and pathogenesis.