title: 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.
abstract: Toll-like receptors (TLRs) have been found to be key elements in pathogen recognition 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 maturation. TLR2 knockout mice and mice carrying a TLR4 mutation (C3H/HeJ) were investigated for DC maturation induced by peptidoglycan (PGN), lipopolysaccharide (LPS), or lipoteichoic acids (LTAs). All stimuli induced maturation of murine bone marrow-derived DCs in control mice. TLR2(-)/- mice lacked maturation upon stimulation with PGN, as assessed by expression of major histocompatibility complex class II, CD86, cytokine, and chemokine production, fluorescein isothiocyanate-dextran uptake, and mixed lymphocyte reactions, while being completely responsive to LPS. A similar lack of maturation was observed in C3H/HeJ mice upon stimulation with LPS. DC maturation induced by LTAs 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 mice. We demonstrate that DC maturation is induced by stimuli from Gram-positive microorganisms, such as PGN and LTA, with similar efficiency as by LPS. Finally, we provide evidence that TLR2 and TLR4 interaction with the appropriate ligand is essential for bacteria-induced maturation of DCs.
authors.affiliation: Institut für Mikrobiologie und Hygiene, University Medical Center Charité, Humboldt-Universität zu Berlin, 10117 Berlin, Germany.
authors.forename: K S
authors.initials: KS
authors.lastname: Michelsen
authors.forename: A
authors.initials: A
authors.lastname: Aicher
authors.forename: M
authors.initials: M
authors.lastname: Mohaupt
authors.forename: T
authors.initials: T
authors.lastname: Hartung
authors.forename: S
authors.initials: S
authors.lastname: Dimmeler
authors.forename: C J
authors.initials: CJ
authors.lastname: Kirschning
authors.forename: R R
authors.initials: RR
authors.lastname: Schumann
mesh_terms: D000818:Animals; D002454:Cell Differentiation / Q000187:drug effects / Q000502:physiology; D002478:Cells, Cultured; D003713:Dendritic Cells / Q000166:cytology* / Q000502:physiology*; D029721:Drosophila Proteins; D008024:Ligands; D008070:Lipopolysaccharides / Q000494:pharmacology; D008562:Membrane Glycoproteins / Q000502:physiology*; D051379:Mice; D011956:Receptors, Cell Surface / Q000502:physiology*; D015398:Signal Transduction / Q000187:drug effects / Q000502:physiology; D051195:Toll-Like Receptor 2; D051197:Toll-Like Receptor 4; D051193:Toll-Like Receptors
chemical_list: D029721:Drosophila Proteins; D008024:Ligands; D008070:Lipopolysaccharides; D008562:Membrane Glycoproteins; D011956:Receptors, Cell Surface; D051195:Toll-Like Receptor 2; D051197:Toll-Like Receptor 4; D051193:Toll-Like Receptors