NADPH oxidase of human dendritic cells: role in Candida albicans killing and regulation by interferons, dectin-1 and CD206.
Human monocyte-derived DC express the enzyme NADPH oxidase, responsible for ROS production. We show that Candida albicans did not activate NADPH oxidase in DC, and was poorly killed by these cells. However, Candida-killing activity increased upon DC stimulation with the NADPH oxidase activator PMA and was further enhanced by DC treatment with IFN-alpha or IFN-gamma. This fungicidal activity took place at high DC-to-Candida ratio, but decreased at low DC-to-yeast ratio, when Candida inhibited the NADPH oxidase by contrasting the assembly of the enzyme on DC plasma membrane. The NADPH oxidase inhibitor diphenyliodonium chloride abrogated the PMA-dependent DC candidacidal capacity. Engagement of beta-glucan receptor dectin-1 induced NADPH oxidase activation in DC that was depressed by mannose-binding receptor CD206 co-stimulation. Candida was internalized by DC through mannose-binding receptors, but not through dectin-1, thus explaining why Candida did not elicit NADPH oxidase activity. Our results indicate that NADPH oxidase is involved in DC Candida-killing activity, which is increased by IFN. However, Candida escapes the oxidative damage by inhibiting NADPH oxidase and by entering DC through receptors not involved in NADPH oxidase activation.
Donini
Marta
M
Department of Pathology, Section of General Pathology, University of Verona, Verona, Italy.
Zenaro
Elena
E
Tamassia
Nicola
N
Dusi
Stefano
S
D002176:Candida albicans / Q000276:immunology*; D003713:Dendritic Cells / Q000201:enzymology* / Q000276:immunology / Q000382:microbiology; D004586:Electrophoresis; D004789:Enzyme Activation / Q000502:physiology; D005434:Flow Cytometry; D006801:Humans; D015151:Immunoblotting; D007372:Interferons / Q000378:metabolism*; D037181:Lectins, C-Type / Q000378:metabolism*; D000090323:Mannose Receptor; D037241:Mannose-Binding Lectins / Q000378:metabolism*; D008565:Membrane Proteins / Q000378:metabolism*; D019255:NADPH Oxidases / Q000378:metabolism*; D009419:Nerve Tissue Proteins / Q000378:metabolism*; D012333:RNA, Messenger / Q000032:analysis; D011956:Receptors, Cell Surface / Q000378:metabolism*; D020133:Reverse Transcriptase Polymerase Chain Reaction; D000099181:Dectin-1
D007372:Interferons; D037181:Lectins, C-Type; D000090323:Mannose Receptor; D037241:Mannose-Binding Lectins; D008565:Membrane Proteins; D019255:NADPH Oxidases; D009419:Nerve Tissue Proteins; D012333:RNA, Messenger; D011956:Receptors, Cell Surface; D000099181:Dectin-1