Differential roles of TLR2 and TLR4 in the host response to Gram-negative bacteria: lessons from a lipopolysaccharide-deficient mutant of Neisseria meningitidis

The inflammatory response to bacterial infections plays an important role i n the detection and elimination of invading micro-organisms. Various compon ents of the bacterial cell wall are capable of activating this pro-inflamma tory response. In the case of Gram-negative bacteria, lipopolysaccharide (L PS) is the dominant trigger, although other bacterial factors are also capa ble of activating this systemic inflammatory response. Recently, Toll-like receptors (TLRs) have been implicated in host responses to bacterial pathog ens. Specifically, TLR4 mediates LPS responses while TLR2 plays a broader r ole in the recognition of a variety of bacteria and bacterial antigens. The experiments in this study were designed to examine the role of Gram-negati ve cell wall components, other than LPS, and their cellular receptors in th e host response to infection using an LPS-deficient mutant of Neisseria men ingitidis. Although less potent than the parental strain, we found the LPS- deficient mutant to be a capable inducer of the inflammatory response in a variety of cell types. Moreover, cellular activation by this mutant require d expression of CD14 and TLR2.