Toll-like receptor 4, but not toll-like receptor 2, is a signaling receptor for Escherichia and Salmonella lipopolysaccharides

Two members of the mammalian Toll-like receptor (TLR) family, TLR2 and TLR4 , have been implicated as receptors mediating cellular activation in respon se 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 asce rtain the relative contribution of these receptors to LPS induced cytokine release. We show that the contribution of TLR2 and TLR4 to LPS-induced cell ular activation correlates with the relative expression levels of these two TLRs in a given cell type. In addition, we have found that significant dif ferences in cell stimulatory activity exist between various smooth and roug h 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 he in agreement with recently published results of others, Upon repurification, none of the commercial LPS preparations ac tivate cells through TLR2, but continue to stimulate cells with comparable activity through TLR4. Our results confirm recent findings that TLR4, but n ot TLR2, mediates cellular activation in response to LPS derived from both Escherichia coli and Salmonella minnesota. Additionally; we show that TLR4 is the predominant signaling receptor for LPS in human whole blood.