Toll-Like Receptor 4,But Not Toll-Like Receptor 2,Is a Signaling Receptor for Escherichia and Salmonella Lipopolysaccharides

摘要

Two members of the mammalian Toll-like receptor (TLR) familty,TLR2 and TLR4,have been implicated as receptors mediating cellular activation in response to bacterial LPS.Through the use of mAbs raised against human TLR2 and TLR4,we have conducted studies in human cell lines and whole blood to ascertain the relative contribution of these receptor4s to LPS induced cytokine release.We show that hte contribution of TLR2 and TLR4 to LPS-induced cellular activationcorrelates with the relative expression levels of these two TLRs in a given cell tupe.In addition,we have found that signficatnt differences in cell stimulatory activity exist between various smooth and rough LPS types that cannot be ascribed to known LPS structural features.These results suggest that impurities in the LPS may be responsible for some of the activity and this would be in agreement with recently published results of others.Upon repurification,none of the commerical LPS prepratations activate cells through TLR2,but continue ot stimulate cells with comparable activity through TLR4.Our results confirm recent findings that TLR4,but not TLR2,mediates celluar activation in response to LPS derived from both Escherichia coli and Salmnella minnseots.Additionally,we show that TLR4 is the predominat signaling receptor for LPS in human whoe blood.