Kensuke Miyake

TL;DR: It is reported that a novel molecule, MD-2, is requisite for LPS signaling of TLR4, which is physically associated withTLR4 on the cell surface and confers responsiveness to LPS.

TL;DR: This is the first report that polysaccharide degradation products of the extracellular matrix produced during inflammation might serve as an endogenous ligand for the TLR-4 complex on DCs.

TL;DR: It is shown that macrophages loaded with synthetic lipid A, E. coli lipopolysaccharide (LPS), or S. typhimurium LPS activate caspase-11 independently of the LPS receptor Toll-like receptor 4 (TLR4), revealing a TLR4-independent mechanism for innate immune recognition of LPS.

TL;DR: It is found that in MD-2−/− embryonic fibroblasts, TLR4 was not able to reach the plasma membrane and predominantly resided in the Golgi apparatus, whereas TLR3 was distributed at the leading edge surface of cells in wild-type embryonic fibrablasts andMD-2 is essential for correct intracellular distribution and LPS-recognition ofTLR4.

TL;DR: A decrease in inflammatory cytokine production in tolerant macrophages well correlates with down-regulation of the surface TLR4 expression, which may explain one of the mechanisms for LPS tolerance.