IgG opsonization of bacteria promotes Th17 responses via synergy between TLRs and FcγRIIa in human dendritic cells.
Dendritic cells (DCs) are essential in inducing adaptive immune responses against bacteria by expressing cytokines that skew T-cell responses toward protective Th17 cells. Although it is widely recognized that induction of these cytokines by DCs involves activation of multiple receptors, it is still incompletely characterized which combination of receptors specifically skews Th17-cell responses. Here we have identified a novel role for FcγRIIa in promoting human Th17 cells. Activation of DCs by bacteria opsonized by serum IgG strongly promoted Th17 responses, which was FcγRIIa-dependent and coincided with enhanced production of selected cytokines by DCs, including Th17-promoting IL-1β and IL-23. Notably, FcγRIIa stimulation on DCs did not induce cytokine production when stimulated individually, but selectively amplified cytokine responses through synergy with TLR2, 4, or 5. Importantly, this synergy is mediated at 2 different levels. First, TLR-FcγRIIa costimulation strongly increased transcription of pro-IL-1β and IL-23p19. Second, FcγRIIa triggering induced activation of caspase-1, which cleaves pro-IL-1β into its bioactive form and thereby enhanced IL-1β secretion. Taken together, these data identified cross-talk between TLRs and FcγRIIa as a novel mechanism by which DCs promote protective effector Th17-cell responses against bacteria.
Department of Cell Biology and Histology, Academic Medical Center, University of Amsterdam, Amsterdam, The Netherlands. j.dendunnen@amc.nl
Jeroen
J
den Dunnen
Lisa T C
LT
Vogelpoel
Tomasz
T
Wypych
Femke J M
FJ
Muller
Leonie
L
de Boer
Taco W
TW
Kuijpers
Sebastiaan A J
SA
Zaat
Martien L
ML
Kapsenberg
Esther C
EC
de Jong
D056704:Adaptive Immunity / Q000276:immunology; D001424:Bacterial Infections / Q000276:immunology*; D002450:Cell Communication / Q000276:immunology; D016207:Cytokines / Q000276:immunology / Q000378:metabolism; D003713:Dendritic Cells / Q000166:cytology / Q000276:immunology* / Q000382:microbiology; D004926:Escherichia coli / Q000276:immunology; D004927:Escherichia coli Infections / Q000276:immunology; D006801:Humans; D007074:Immunoglobulin G / Q000276:immunology*; D008024:Ligands; D008264:Macrophages / Q000166:cytology / Q000276:immunology / Q000382:microbiology; D020239:Receptor Cross-Talk / Q000276:immunology; D017452:Receptors, IgG / Q000276:immunology*; D012480:Salmonella Infections / Q000276:immunology; D012486:Salmonella typhimurium / Q000276:immunology; D013203:Staphylococcal Infections / Q000276:immunology; D013211:Staphylococcus aureus / Q000276:immunology; D013212:Staphylococcus epidermidis / Q000276:immunology; D058504:Th17 Cells / Q000166:cytology / Q000276:immunology* / Q000382:microbiology; D051193:Toll-Like Receptors / Q000276:immunology*
D016207:Cytokines; C080568:Fc gamma receptor IIA; D007074:Immunoglobulin G; D008024:Ligands; D017452:Receptors, IgG; D051193:Toll-Like Receptors