title: Toll receptor-mediated regulation of NADPH oxidase in human dendritic cells.
abstract: Activation of NADPH oxidase represents an essential mechanism of defense against pathogens. Dendritic cells (DC) are phagocytic cells specialized in Ag presentation rather than in bacteria killing. Human monocyte-derived DC were found to express the NADPH oxidase components and to release superoxide anions in response to phorbol esters and phagocytic agonists. The NADPH oxidase components p47phox and gp91phox were down-regulated during monocyte differentiation to DC, and maturation of DC with pathogen-derived molecules, known to activate TLRs, increased p47phox and gp91phox expression and enhanced superoxide anions release. Similar results were obtained with plasmacytoid DC following maturation with influenza virus. In contrast, activation of DC by immune stimuli (CD40 ligand) did not regulate NADPH oxidase components or respiratory burst. NADPH oxidase-derived oxygen radicals did not play any role in DC differentiation, maturation, cytokine production, and induction of T cell proliferation, as based on the normal function of DC generated from chronic granulomatous disease patients and the use of an oxygen radical scavenger. However, NADPH oxidase activation was required for DC killing of intracellular Escherichia coli. It is likely that the selective regulation of oxygen radicals production by pathogen-activated DC may function to limit pathogen dissemination during DC trafficking to secondary lymphoid tissues.
authors.affiliation: Istituto di Ricerche Farmacologiche "Mario Negri," Milan, Italy.
authors.forename: Marisa
authors.initials: M
authors.lastname: Vulcano
authors.forename: Stefano
authors.initials: S
authors.lastname: Dusi
authors.forename: Daniele
authors.initials: D
authors.lastname: Lissandrini
authors.forename: Raffaele
authors.initials: R
authors.lastname: Badolato
authors.forename: Paola
authors.initials: P
authors.lastname: Mazzi
authors.forename: Elena
authors.initials: E
authors.lastname: Riboldi
authors.forename: Elena
authors.initials: E
authors.lastname: Borroni
authors.forename: Angelica
authors.initials: A
authors.lastname: Calleri
authors.forename: Marta
authors.initials: M
authors.lastname: Donini
authors.forename: Alessandro
authors.initials: A
authors.lastname: Plebani
authors.forename: Luigi
authors.initials: L
authors.lastname: Notarangelo
authors.forename: Tiziana
authors.initials: T
authors.lastname: Musso
authors.forename: Silvano
authors.initials: S
authors.lastname: Sozzani
mesh_terms: D000293:Adolescent; D000328:Adult; D002454:Cell Differentiation / Q000276:immunology; D045744:Cell Line, Tumor; D002478:Cells, Cultured; D002648:Child; D002675:Child, Preschool; D003713:Dendritic Cells / Q000201:enzymology* / Q000276:immunology* / Q000378:metabolism / Q000473:pathology; D004926:Escherichia coli / Q000254:growth & development / Q000276:immunology; D005260:Female; D006105:Granulomatous Disease, Chronic / Q000276:immunology / Q000382:microbiology / Q000473:pathology; D006801:Humans; D007424:Intracellular Fluid / Q000276:immunology / Q000382:microbiology; D008024:Ligands; D008070:Lipopolysaccharides / Q000494:pharmacology; D008562:Membrane Glycoproteins / Q000378:metabolism / Q000502:physiology*; D019255:NADPH Oxidases / Q000378:metabolism* / Q000502:physiology; D010587:Phagocytosis / Q000276:immunology; D011956:Receptors, Cell Surface / Q000378:metabolism / Q000502:physiology*; D016897:Respiratory Burst / Q000276:immunology; D051193:Toll-Like Receptors; D015854:Up-Regulation / Q000276:immunology
chemical_list: D008024:Ligands; D008070:Lipopolysaccharides; D008562:Membrane Glycoproteins; D011956:Receptors, Cell Surface; D051193:Toll-Like Receptors; D019255:NADPH Oxidases