Ceramide, membrane rafts and infections.

Distinct domains in the cell membrane, termed rafts, emerge as central for the infection of mammalian cells by many pathogens. Rafts consist of sphingolipids and cholesterol that interact strongly, and thus spontaneously separate from other phospholipids in the cell membrane. Recent studies suggest that at least some pathogens activate the acid sphingomyelinase that releases ceramide in membrane rafts. The generation of ceramide transforms small rafts into a signaling unit and results in the fusion of small rafts to large platforms. Membrane rafts and ceramide-enriched membrane platforms have been shown to mediate internalization of bacteria, viruses and parasites into the host cell, to initiate apoptosis of the host cell upon infection and to regulate the release of cytokines from infected mammalian cells. Furthermore, rafts and ceramide have been implicated in the intracellular trafficking of phagosomes and in the budding of viruses from infected cells. The molecular function of rafts and ceramide-enriched membrane platforms seems to be the re-organization of receptor and intracellular signaling molecules in the cell membrane permitting the interaction of the pathogen with the cell. This suggests that rafts and ceramide-enriched membrane platforms function as central structures involved in the infection of mammalian cells by pathogens and as targets for the development of anti-infective drugs. Copyright 2004 Springer-Verlag