MD-2 binds to the LPS monomer and is sensitive to the acylation pattern of the lipid A moiety. Association of the MD-2:LPS complex to the ectodomain of the TLR4 finally transduces the signal through the association of intracellular TIR domain, recruiting the adapter proteins triggering the signaling cascade (20) . In a similar way to TLR2, TLR4 uses the myeloid differentiation primary-response gene 88 adapter like protein (MAL) as a bridging adaptor to recruit the myeloid differentiation primary-response gene 88 (MyD88) to activate the NF-κB, p38 and JNK/MAPK pathways via TRAF6 (9) . MAL is recruited to plasma membrane microdomains containing the phospholipid PtdIns (4,5)P 2 (phosphatidylinositol-4,5-bisphosphate). MAL subsequently recruits MyD88 (20) . Another pathway activated by TLR4 involves TRIF-related adaptor molecule (TRAM). Similar to MAL, TRAM is also membrane proximal and requires myristoylation to lodge into the membrane. TRAM recruits the Toll/interleukin-1 receptor (TIR)-domain-containing adaptor protein inducing interferonβ (TRIF) which activates the tumor-necrosis factor-receptorassociated factor 3 (TRAF3), TRAF6 and receptor interacting protein 1(RIP1). Recent work with CD14 knockout mice suggested that TRL4 can function in two ways: one where full signaling occurs in the presence of CD14 and one limited to MyD88-dependent signaling (21) .