Downregulation of dendritic cells functions by Neutrophil Extracellular Traps
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1
INSERM UMR-S 996, France
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2
Stallergènes, France
Neutrophils are key components of the innate response via several mechanisms, in particular the production of Neutrophil Extracellular Traps (NETs), chromatin fibers associated with granule and cytoplasmic proteins that play important roles in antimicrobial defenses but seem also involved in some auto-immune and inflammatory diseases.
Our aim was to investigate whether NETs could interact with dendritic cell (DC) maturation and modulate adaptive immunity.
We first developed a model to induce, isolate and characterize NETs from human blood neutrophils. Calcium ionophore A23187 was chosen to induce NETs and the restriction enzyme Alu I allowed the recovery of heterogeneous-sized fragments of NETs. The presence of dsDNA and proteins was shown and, using western-blotting, NET major proteins (lactoferrin, histone 3, citrullinated histone 3) could be quantified. Finally, these isolated-NET were active as they were able to kill bacteria.
The co-culture of isolated-NETs preparations with DC alone did not induce DC maturation as measured by phenotypic modifications and cytokine productions. By contrast, NETs induced a significant decrease of LPS-induced expression of CD86, CD83, CD80, CD40 and HLA-DR, as well as TNF, IL12-p70, IL23, IL8, IL6 and IL-10 release. This downregulation of LPS-induced DC maturation led to a decrease of T lymphocyte proliferation (allogenic model) and is associated with a markedly reduction of IFNgamma and IL17 while promoting IL5 and IL13.
Our data suggest that, in our model, the NETs produced during inflammation can participate to the regulation of DC activation and maturation in order to potentially limit excessive immune responses.
Keywords:
neutrophil extracellular traps (NETs),
Dendritic Cells,
Neutrophils,
Down-Regulation,
polarization T
Conference:
15th International Congress of Immunology (ICI), Milan, Italy, 22 Aug - 27 Aug, 2013.
Presentation Type:
Abstract
Topic:
Adaptive Immunity
Citation:
Barrientos
L,
Marin-Esteban
V,
Gorges
R,
Gueguen
C,
De-Chaisemartin
L,
Sandre
C,
Mascarell
L,
Kerdine-Romer
S,
Pallardy
M and
Chollet-Martin
S
(2013). Downregulation of dendritic cells functions by Neutrophil Extracellular Traps.
Front. Immunol.
Conference Abstract:
15th International Congress of Immunology (ICI).
doi: 10.3389/conf.fimmu.2013.02.00710
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Received:
13 Jun 2013;
Published Online:
22 Aug 2013.
*
Correspondence:
Prof. Sylvie Chollet-Martin, INSERM UMR-S 996, Chatenay-Malabry, France, sylvie.chollet-martin@u-psud.fr