Requirement of phospholipase C-gamma2 (PLCgamma2) for Dectin-1-induced antigen presentation and induction of TH1/TH17 polarization.
DC recognize microbial components through an array of receptors known as PRR. PRR initiate intracellular signals, which engender DC with the capacity to stimulate T-cell responses. Dectin-1 is a PRR that recognizes beta-glucan, a major constituent of many fungi's outer cell wall. Here we show that Dectin-1 activates DC through phospholipase (PLC)gamma2 signaling. PLCgamma2-deficient DC were unable to expand antigen-specific T cells and induce T(H)1 and T(H)17 differentiation in response to beta-glucan. Mechanistically, PLCgamma2-deficiency impaired the capacity of DC to secrete polarizing cytokines following exposure to beta-glucan. Dectin-1 required PLCgamma2 to activate MAPK, AP-1 and NF-kappaB, which induce cytokine gene expression. Moreover, PLCgamma2 controlled Dectin-1-mediated NFAT activation and induction of NFAT-dependent genes such as IL-2, cyclooxigenase-2 and Egr transcription factors. We conclude that PLCgamma2 is a crucial signaling mediator that modifies DC gene expression program to activate DC responses to beta-glucan-containing pathogens.
Tassi
Ilaria
I
Department of Pathology and Immunology, Washington University School of Medicine, St. Louis, MO 63110, USA.
Cella
Marina
M
Castro
Iris
I
Gilfillan
Susan
S
Khan
Wasif N
WN
Colonna
Marco
M
D000818:Animals; D017951:Antigen Presentation / Q000276:immunology*; D002454:Cell Differentiation / Q000276:immunology; D003713:Dendritic Cells / Q000201:enzymology / Q000276:immunology*; D024202:Electrophoretic Mobility Shift Assay; D007113:Immunity, Innate / Q000276:immunology; D020381:Interleukin-17 / Q000235:genetics / Q000276:immunology*; D037181:Lectins, C-Type; D008565:Membrane Proteins / Q000276:immunology*; D051379:Mice; D018345:Mice, Knockout; D016328:NF-kappa B / Q000276:immunology; D050778:NFATC Transcription Factors / Q000276:immunology; D009419:Nerve Tissue Proteins / Q000276:immunology*; D051966:Phospholipase C gamma / Q000276:immunology*; D018417:Th1 Cells / Q000276:immunology*; D018808:Transcription Factor AP-1 / Q000276:immunology; D047071:beta-Glucans / Q000276:immunology; D000099181:Dectin-1
D020381:Interleukin-17; D037181:Lectins, C-Type; D008565:Membrane Proteins; D016328:NF-kappa B; D050778:NFATC Transcription Factors; D009419:Nerve Tissue Proteins; D051966:Phospholipase C gamma; D018808:Transcription Factor AP-1; D047071:beta-Glucans; D000099181:Dectin-1