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 lipopolysaccharide-binding protein (LBP) derived from respiratory epithelial cells 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 the stationary phase bound more LBP than did log-phase bacteria. Of interest, as few as 1 LBP-bearing bacterium/cell induced strong signaling through TLR4. In contrast, LBP bound to NTI-Ii did not promote any increased signaling mediated by TLR2, compared with NTHi without LBR These data suggest that, upon NTHi infection, low numbers of bacteria binding LBP may activate TLR4-bearing cells, such as alveolar macrophages, and consequently induce an inflammatory response.