Membrane-associated proteins of a lipopolysaccharide-deficient mutant of Neisseria meningitidis activate the inflammatory response through toll-like receptor 2

The recent isolation of a lipopolysaccharide (LPS)-deficient mutant of Neis seria meningitidis has allowed us to explore the roles of other gram-negati ve cell wall components in the host response to infection. The experiments in this study were designed to examine the ability of this mutant strain to activate cells. Although it was clearly less potent than the parental stra in, we found the LPS-deficient mutant to be a capable inducer of the inflam matory response in monocytic cells, inducing a response similar to that see n with Staphylococcus aureus. Cellular activation by the LPS mutant was rel ated to expression of CD14, a high-affinity receptor for LPS and other micr obial products, as well as Toll-like receptor 2, a member of the Toll famil y of receptors recently implicated in host responses to gram positive bacte ria. In contrast to the parental strain, the synthetic LPS antagonist E5564 did not inhibit the LPS-deficient mutant. We conclude that even in the abs ence of LPS, the gram-negative cell wall remains a potent inflammatory stim ulant, utilizing signaling path wags independent of those involved in LPS s ignaling.