The role of toll-like receptors (TLRs) in bacteria-induced maturation of murine dendritic cells (DCs) - Peptidoglycan and lipoteichoic acid are inducers of DC maturation and require TLR2

Toll-like receptors (TLRs) have been found to be key elements in pathogen r ecognition by the host immune system. Dendritic cells (DCs) are crucial for both innate immune responses and initiation of acquired immunity, Here we focus on the potential involvement of TLR ligand interaction in DC maturati on. TLR2 knockout mice and mice carrying a TLR4 mutation (C3H/HeJ) were inv estigated for DC maturation induced by peptidoglycan (PGN), lipopolysacchar ide (LPS), or lipoteichoic acids (LTAs), All stimuli induced maturation of murine bone marrow-derived DCs in control mice. TLR2(-/-) mice lacked matur ation upon stimulation with PGN, as assessed by expression of major histoco mpatibility complex class II, CD86, cytokine, and chemokine production, flu orescein isothiocyanate-dextran uptake, and mixed lymphocyte reactions, whi le being completely responsive to LPS. A similar lack of maturation was obs erved in C3H/HeJ mice upon stimulation with LPS, DC maturation induced by L TAs from two different types of bacteria was severely impaired in TLR2(-/-) , whereas C3H/HeJ mice responded to LTAs in a manner similar to wild-type m ice, We demonstrate that DC maturation is induced by stimuli from Gram-posi tive microorganisms, such as PGN and LTA, with similar efficiency as by LPS , Finally, we provide evidence that TLR2 and TLR4 interaction with the appr opriate ligand is essential for bacteria-induced maturation of DCs.