Toll receptor-mediated regulation of NADPH oxidase in human dendritic cells.
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.
Vulcano
Marisa
M
Istituto di Ricerche Farmacologiche "Mario Negri," Milan, Italy.
Dusi
Stefano
S
Lissandrini
Daniele
D
Badolato
Raffaele
R
Mazzi
Paola
P
Riboldi
Elena
E
Borroni
Elena
E
Calleri
Angelica
A
Donini
Marta
M
Plebani
Alessandro
A
Notarangelo
Luigi
L
Musso
Tiziana
T
Sozzani
Silvano
S
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
D008024:Ligands; D008070:Lipopolysaccharides; D008562:Membrane Glycoproteins; D011956:Receptors, Cell Surface; D051193:Toll-Like Receptors; D019255:NADPH Oxidases