Host-cell lipid rafts: a safe door for micro-organisms?

Abstract

The lipid raft hypothesis proposed that these microdomains are small (10-200 nM), highly dynamic and enriched in cholesterol, glycosphingolipids and signalling phospholipids, which compartmentalize cellular processes. These membrane regions play crucial roles in signal transduction, phagocytosis and secretion, as well as pathogen adhesion/interaction. Throughout evolution, many pathogens have developed mechanisms to escape from the host immune system, some of which are based on the host membrane microdomain machinery. Thus lipid rafts might be exploited by pathogens as signalling and entry platforms. In this review, we summarize the role of lipid rafts as players in the overall invasion process used by different pathogens to escape from the host immune system.

Figure 1

Membrane microdomains (a) A classical lipid‐raft scheme. Membrane microdomains are enriched with cholesterol and sphingolipids and also possess associated proteins such as GPI‐anchored protein. (b) A caveolin‐rich lipid‐raft scheme. The membrane microdomain can form invaginations called caveolae. Caveolin is a marker protein of caveolae structure.

Figure 2

Pathogen—raft interaction Several pathogens can directly interact with different target cells through membrane microdomains in different manners. It is known that the entry via lipid rafts can avoid lysosomal fusion and therefore allow pathogen survival. In addition, parasites might modulate signalling pathways, including lipid‐raft‐associated protein kinases [Srfk (Src family kinases)]. Especially viruses, which do not have their own protein synthesis machinery, target the ER after subverting the lysosomal pathway. Lys, lysosome; PV, parasitophorous vacuole.

Figure 3

P2X₇ receptor and TLR interaction with lipid rafts (a) P2X₇ receptor (P2X₇R) and/or TLR activation, by ATP or PAMPs respectively, in non‐raft membrane regions. (b) These receptors, when stimulated, migrate to lipid‐raft domains. In addition, the P2X₇R is involved with inflammatory immune response, as well as TLRs which are related to the initial signal to the immune response. Thus it is suggested that the action of both receptors, together within lipid rafts, can lead to a more intense immune response. MyD88, myeloid differentiation primary response gene 88.