PMID- 22649103
OWN - NLM
STAT- MEDLINE
DCOM- 20120918
LR  - 20210202
IS  - 1528-0020 (Electronic)
IS  - 0006-4971 (Linking)
VI  - 120
IP  - 1
DP  - 2012 Jul 5
TI  - IgG opsonization of bacteria promotes Th17 responses via synergy between TLRs and 
      FcgammaRIIa in human dendritic cells.
PG  - 112-21
LID - 10.1182/blood-2011-12-399931 [doi]
AB  - 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 FcgammaRIIa in promoting human 
      Th17 cells. Activation of DCs by bacteria opsonized by serum IgG strongly 
      promoted Th17 responses, which was FcgammaRIIa-dependent and coincided with enhanced 
      production of selected cytokines by DCs, including Th17-promoting IL-1beta and 
      IL-23. Notably, FcgammaRIIa 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-FcgammaRIIa costimulation strongly increased 
      transcription of pro-IL-1beta and IL-23p19. Second, FcgammaRIIa triggering induced 
      activation of caspase-1, which cleaves pro-IL-1beta into its bioactive form and 
      thereby enhanced IL-1beta secretion. Taken together, these data identified 
      cross-talk between TLRs and FcgammaRIIa as a novel mechanism by which DCs promote 
      protective effector Th17-cell responses against bacteria.
FAU - den Dunnen, Jeroen
AU  - den Dunnen J
AD  - Department of Cell Biology and Histology, Academic Medical Center, University of 
      Amsterdam, Amsterdam, The Netherlands. j.dendunnen@amc.nl
FAU - Vogelpoel, Lisa T C
AU  - Vogelpoel LT
FAU - Wypych, Tomasz
AU  - Wypych T
FAU - Muller, Femke J M
AU  - Muller FJ
FAU - de Boer, Leonie
AU  - de Boer L
FAU - Kuijpers, Taco W
AU  - Kuijpers TW
FAU - Zaat, Sebastiaan A J
AU  - Zaat SA
FAU - Kapsenberg, Martien L
AU  - Kapsenberg ML
FAU - de Jong, Esther C
AU  - de Jong EC
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20120530
PL  - United States
TA  - Blood
JT  - Blood
JID - 7603509
RN  - 0 (Cytokines)
RN  - 0 (Fc gamma receptor IIA)
RN  - 0 (Immunoglobulin G)
RN  - 0 (Ligands)
RN  - 0 (Receptors, IgG)
RN  - 0 (Toll-Like Receptors)
SB  - IM
MH  - Adaptive Immunity/immunology
MH  - Bacterial Infections/*immunology
MH  - Cell Communication/immunology
MH  - Cytokines/immunology/metabolism
MH  - Dendritic Cells/cytology/*immunology/microbiology
MH  - Escherichia coli/immunology
MH  - Escherichia coli Infections/immunology
MH  - Humans
MH  - Immunoglobulin G/*immunology
MH  - Ligands
MH  - Macrophages/cytology/immunology/microbiology
MH  - Receptor Cross-Talk/immunology
MH  - Receptors, IgG/*immunology
MH  - Salmonella Infections/immunology
MH  - Salmonella typhimurium/immunology
MH  - Staphylococcal Infections/immunology
MH  - Staphylococcus aureus/immunology
MH  - Staphylococcus epidermidis/immunology
MH  - Th17 Cells/cytology/*immunology/microbiology
MH  - Toll-Like Receptors/*immunology
EDAT- 2012/06/01 06:00
MHDA- 2012/09/19 06:00
CRDT- 2012/06/01 06:00
PHST- 2012/06/01 06:00 [entrez]
PHST- 2012/06/01 06:00 [pubmed]
PHST- 2012/09/19 06:00 [medline]
AID - S0006-4971(20)47577-9 [pii]
AID - 10.1182/blood-2011-12-399931 [doi]
PST - ppublish
SO  - Blood. 2012 Jul 5;120(1):112-21. doi: 10.1182/blood-2011-12-399931. Epub 2012 May 
      30.