title: Inverse correlation of maturity and antibacterial activity in human dendritic cells.
abstract: Dendritic cells (DCs) are a key part of host defense against microbial pathogens, being part of the innate immune system, but also instructing the adaptive T cell response. This study was designed to evaluate whether human DCs directly contribute to innate immunity by killing intracellular bacteria, using tuberculosis as a model. DCs were detected in bronchoalveolar lavage samples indicating that DCs are available for immediate interaction with Mycobacterium tuberculosis (M. Tb) after inhalation of the pathogen. The phenotype of DC in bronchoalveolar lavage closely resembles monocyte-derived immature DC (iDC) according to the expression of CD1a, CD83, and CCR7. The antimicrobial activity of iDC against intracellular M. Tb inversely correlated with TNF-alpha-release and was enhanced by treatment with anti-TNF-alpha Abs. Differentiation of iDC into mature DC by addition of TNF-alpha or activation via Toll-like receptors further reduced killing of M. Tb. The antibacterial activity against intracellular M. Tb of all DCs was significantly lower than alveolar macrophages. Therefore, the maintenance of a pool of DCs at the site of disease activity in tuberculosis, and the maturation of these DC by TNF-alpha provides a mechanism by which M. Tb escapes the innate immune system.
authors.affiliation: Institut für Klinische Mikrobiologie, Immunologie und Hygiene, Universität Erlangen-Nürnberg, Erlangen, Germany.
authors.forename: Maike
authors.initials: M
authors.lastname: Buettner
authors.forename: Christoph
authors.initials: C
authors.lastname: Meinken
authors.forename: Max
authors.initials: M
authors.lastname: Bastian
authors.forename: Rauf
authors.initials: R
authors.lastname: Bhat
authors.forename: Elmar
authors.initials: E
authors.lastname: Stössel
authors.forename: Gerhard
authors.initials: G
authors.lastname: Faller
authors.forename: George
authors.initials: G
authors.lastname: Cianciolo
authors.forename: Joachim
authors.initials: J
authors.lastname: Ficker
authors.forename: Manfred
authors.initials: M
authors.lastname: Wagner
authors.forename: Martin
authors.initials: M
authors.lastname: Röllinghoff
authors.forename: Steffen
authors.initials: S
authors.lastname: Stenger
mesh_terms: D001419:Bacteria / Q000254:growth & development / Q000276:immunology*; D018893:Bronchoalveolar Lavage; D002454:Cell Differentiation; D002478:Cells, Cultured; D003713:Dendritic Cells / Q000166:cytology* / Q000276:immunology*; D006801:Humans; D007113:Immunity, Innate; D016130:Immunophenotyping; D016676:Macrophages, Alveolar / Q000276:immunology; D009169:Mycobacterium tuberculosis / Q000254:growth & development / Q000276:immunology; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism
chemical_list: D014409:Tumor Necrosis Factor-alpha