Human Toll-like receptor 2 mediates monocyte activation by Listeria monocytogenes, but not by group B streptococci or lipopolysaccharide

Human Toll like receptor (TLR) 2 has been implicated as a signaling recepto r for LPS from Gram-negative bacteria and cell wall components from Gram-po sitive organisms, In this study, we investigated whether TLR2 can signal ce ll activation by the heat-killed group B streptococci type III (GBS) and Li steria monocytogenes (HKLM), HKLM, but not GBS, showed a time- and dose-dep endent activation of Chinese hamster ovary cells transfected with human TLR 2, as measured by translocation of NF-kappa B and induction of IL-6 product ion, A mAb recognizing a TLR2-associated epitope (TL2.1) was generated that inhibited IL-6 production from Chinese hamster ovary-TLR2 cells stimulated with HKLM or LPS, The TL2.1 mAb reduced HKLM-induced TNF production from h uman monocytes by 60%, whereas a CD14 mAb (3C10) reduced the TNF production by 30%, However, coadministrating TL2.1 and 3C10 inhibited the TNF respons e by 80%, In contrast to this, anti-CD14 blocked LPS induced TNF production from monocytes, whereas anti-TLR2 showed no inhibition. Neither TL2.1 nor 3C10 affected GBS-induced TNF production. These results show that TLR2 can function as a signaling receptor for HKLM, possibly together with CD14, but that TLR2 is unlikely to be involved in cell activation by GBS, Furthermor e, although LPS can activate transfected cell lines through TLR2, this rece ptor does not seem to be the main transducer of LPS activation of human mon ocytes, Thus, our data demonstrate the ability of TLR2 to distinguish betwe en different pathogens. The Journal of Immunology, 2000, 164: 2064-2069.