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 superoside 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 gp91 phox 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.
| Original language | English |
|---|---|
| Pages (from-to) | 5749-5756 |
| Number of pages | 8 |
| Journal | Journal of Immunology |
| Volume | 173 |
| Issue number | 9 |
| Publication status | Published - Nov 1 2004 |
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ASJC Scopus subject areas
- Immunology
Cite this
Toll receptor-mediated regulation of NADPH oxidase in human dendritic cells. / Vulcano, Marisa; Dusi, Stefano; Lissandrini, Daniele; Badolato, Raffaele; Mazzi, Paola; Riboldi, Elena; Borroni, Elena; Calleri, Angelica; Donini, Marta; Plebani, Alessandro; Notarangelo, Luigi; Musso, Tiziana; Sozzani, Silvano.
In: Journal of Immunology, Vol. 173, No. 9, 01.11.2004, p. 5749-5756.Research output: Contribution to journal › Article
}
TY - JOUR
T1 - Toll receptor-mediated regulation of NADPH oxidase in human dendritic cells
AU - Vulcano, Marisa
AU - Dusi, Stefano
AU - Lissandrini, Daniele
AU - Badolato, Raffaele
AU - Mazzi, Paola
AU - Riboldi, Elena
AU - Borroni, Elena
AU - Calleri, Angelica
AU - Donini, Marta
AU - Plebani, Alessandro
AU - Notarangelo, Luigi
AU - Musso, Tiziana
AU - Sozzani, Silvano
PY - 2004/11/1
Y1 - 2004/11/1
N2 - 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 superoside 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 gp91 phox 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.
AB - 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 superoside 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 gp91 phox 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.
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M3 - Article
C2 - 15494527
AN - SCOPUS:6344273114
VL - 173
SP - 5749
EP - 5756
JO - Journal of Immunology
JF - Journal of Immunology
SN - 0022-1767
IS - 9
ER -