Figure 1.

Role of cholesterol efflux in innate immune cell activation. (A) TLR4, which is expressed in innate immune cells including monocytes, macrophages and dendritic cells, is activated by lipopolysaccharide (LPS). These cells express also high amounts of CD14, which facilitates the activation of TLR4 by LPS. LPS induces a transient TLR4 trafficking to lipid rafts; following dimerization, a process required for the initiation of signaling during innate immune response, TLR4 triggers the MyD88-dependent signaling pathway, leading to the production of pro-inflammatory cytokines and cell activation. ApoA-I and HDL, as well as apoE, may dampen inflammation by selectively reducing the free cholesterol content in lipid rafts and the consequent chance of an MyD88-dependent TLR trafficking to lipid rafts in cells exposed to LPS. PL: phospholipids. (B) In resting T-cells, TCR is localized in non-raft domains of plasma membrane in monomeric form. Cholesterol is imported into the cell LDL; when TCRs become antigen stimulated, they associate with lipid rafts, thus resulting in the activation of downstream signaling pathways and consequent T cell proliferation. ApoA-I and HDL, by removing cholesterol from cell membrane, may modulate the abundance of lipid rafts and their content of cholesterol, thus controlling T cell immune response.