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2017 ; 8
(ä): 523
Nephropedia Template TP
Guimarães-Costa AB
; Rochael NC
; Oliveira F
; Echevarria-Lima J
; Saraiva EM
Front Immunol
2017[]; 8
(ä): 523
PMID28567039
show ga
Monocyte-derived dendritic cells (mo-DCs) are essential for the development of a
Th1 protective immune response against Leishmania parasites. It is well known
that IL-4 and GM-CSF drive differentiation of human monocytes to dendritic cells
(DCs). Here, we investigate if neutrophil extracellular traps (NETs) disrupt this
process. NETs-enriched supernatants, generated after human neutrophil activation
by Leishmania promastigotes, were added to monocytes and differentiation
monitored by expression of molecules associated with macrophage and DCs
phenotypes, cytokine production, and parasite killing. We found that NETs
addition to IL-4/GM-CSF-treated monocytes prevented then to fully differentiate
into DCs. No effect was observed if NETs were treated with DNase or by filtering
the traps. Moreover, NETs closely interact with monocytes and downregulate the
expression of the IL-4 receptor, which in turn disrupts fully differentiation of
monocytes into DCs. Neutrophil elastase inhibition rescues the monocytes to DCs
differentiation. Monocytes cultured with IL-4/GM-CSF and NETs differentiated into
macrophages, as observed by the increased expression of CD68, CD32, and CD163,
and decreased expression of CD80. Moreover, NET addition to IL-4/GM-CSF-treated
monocytes rendered these cells less efficient to kill Leishmania parasites.
Altogether, our results show that NETs interfere with IL-4/GM-CSF driven
differentiation, reprogramming the generation of mo-DCs to an anti-inflammatory
macrophage.