Lipopolysaccharide-binding protein increases toll-like receptor 4-dependent activation by nontypeable Haemophilus influenzae

Nontypeable Haemophilus influenzae (NTHi) is a common cause of respiratory tract infections. This study investigated the ability of NTHi to bind lipop olysaccharide-binding protein (LBP) derived from respiratory epithelial cel ls and the subsequent stimulation of transfected cells expressing membrane- bound CD14 and toll-like receptor 2 (TLR2) or TLR4. In the absence of LBP, NTHi at high concentrations (100 bacteria/epithelial cell) were required to induce signals through TLR2 and TLR4. Flow cytometry showed that NTHi in t he stationary phase bound more LBP than did log-phase bacteria. Of interest , as few as 1 LBP-bearing bacterium/cell induced strong signaling through T LR4. In contrast, LBP bound to NTI-Ii did not promote any increased signali ng mediated by TLR2, compared with NTHi without LBR These data suggest that , upon NTHi infection, low numbers of bacteria binding LBP may activate TLR 4-bearing cells, such as alveolar macrophages, and consequently induce an i nflammatory response.