Abstract

The recognition of bacterial products, such as lipopolysaccharide (LPS) by the innate immune system lead to a strong pro-inflammatory response that can eventually lead to fatal sepsis syndrome in humans. Although CD14 and TLR4 have been identified as the key molecules involved in LPS-induced signal transduction, accumulating evidence indicates that multiple receptors are also involved. Our group has recently identified a cluster of receptors, involving heat-shock proteins 70 and 90, chemokine receptor 4 as well as growth differentiation factor 5, that are formed following LPS stimulation. In addition, we present data demonstrating that these molecules associate with TLR4 and accumulate in membrane microdomains following LPS ligation. Our results suggest that the entire bacterial recognition is based around the recruitment of multiple signalling molecules, in addition to CD14 and TLRs, within the lipid rafts. We propose that different combinational associations of receptors within activation clusters determine the different responses to a variety of bacterial stimuli.