Other bacterial components may also act as PAMPs. DCs are the most potent antigen presenting cells that initiate and amplify immune responses. Maturation of DCs by PAMPs enables DCs to convey pathogen-associated signals to the adaptive immune system. In this report, we showed that the meningococcal PBP2 can trigger DC maturation through TLR4. PBP2 is a major enzyme involved in the biosynthesis of meningococcal peptidoglycan, most likely by acting as a transpeptidase. Its alteration can modify the structure of peptidoglycan and impact hence on Nod-dependant signalling. It is therefore of interest that PBP2 itself can also directly signal through TLR4. Meningococcal components can hence modulate signalling to host cells and the host’s genetic factors can also determine the clinical MF63 Abmole mPGES-1 in prostate cancer controls stemness and amplifies EGFR-1 driven oncogenicity outcome of meningococcal infection. Interestingly, it has been shown that individuals with rare Abmole MG132 mutations in TLR4 increase the risk of systemic meningococcal disease. In addition to meningococcal lipooligosaccharide (LOS), PBP2 may also be a relevant and direct player in hostpathogen interactions through TLR4 that influence the clinical outcome of meningococcal infection. Although the canonical TLR4 activator is a liposacharidic structure such as LPS, it is interesting to note that several proteins have been shown to activate this receptor. Indeed, mammalian endogenous proteins such as Tenascin-C and HMGB1 have been described as TLR4 ligands among others. Moreover, F-protein from respiratory syncytial virus (RSV) and FimH adhesion from type 1 fimbriae have been reported to induce DC maturation through TLR4. We directly demonstrate through two different approaches that PBP2 binds human TLR4. This observation opens the exciting perspective of analyzing how this interaction takes place at the molecular level. We observed that neither meningococcal PBP1 nor PBP2 from H. pylori could interact with TLR4. Moreover, mutant PBP2 harbouring mutations in the penicillin binding domain, was as effective as WT PBP2 in inducing DC maturation (unpublished observations). We can therefore conclude that the penicillin-binding domain is most likely not involved in TLR4/meningococcal PBP2 interaction.