Location, Location, Location: Is Membrane Partitioning Everything When It Comes to Innate Immune Activation?

Figure 1

Activation of TLRs and adjuvant receptors on cell surface before and after stimulation by bacterial products. (a) TLR2 forms heterodimers with TLR1 and TLR6 on the cell surface and these heterodimer preexist and are not induced by the ligand. These heterodimers do not reside in lipid rafts before stimulation but are recruited to lipid rafts upon stimulation. This process is independent of signaling and facilitates the trafficking of TLRs from the cell surface to the Golgi. (b) TLR2/6 heterodimers are recruited within lipid rafts and associate with lipid raft-resident proteins CD14 and CD36 upon ligand stimulation. Binding of an appropriate microbial substance leads to energy-dependent clustering of heterotypic receptors and activation of intracellular signaling cascades that lead via NF-κB to the production and secretion of proinflammatory cytokines.