Multiple aspects of our studies of live SE are novel: a) SE (and SE-S) activates cytokine production via TLR2 in human whole blood, b) TLR2 is particularly important in detecting low concentrations of SE in primary murine macrophages, whereas high concentrations of SE can activate these cells in a TLR2-independent manner, c) TLR2 mediates early (1 h) cytokine production after i.v. challenge with SE in vivo and d) TLR2 plays a crucial and selective role in mediating subsequent clearance of SE bacteremia at 24–48 h in vivo. This evidence concerns the gene TLR2 and bacterial infectious disease with sepsis.