N. meningitidis LOS seems to induce a proinflammatory cytokine response either independently or through the CD14/Toll-like receptor 4 (TLR4) pathway. This CD14/TLR4 activation requires the KDO moiety. Meningococcal lipid A expressed by KDO-deficient meningococci is much less biologically active than (KDO)2-containing meningococcal LOS. The impact on inflammatory responses of different meningococcal LOSs has been analyzed under ex vivo conditions using cell lines or peripheral blood mononuclear cells. It was shown that lpxA mutants may be less toxic due to a reduced capacity to induce tumor necrosis factor alpha (TNF-α), although they were still able to induce a significant inflammatory response.