Neutrophil Extracellular Traps Downregulate Lipopolysaccharide-Induced Activation of Monocyte-Derived Dendritic Cells

Barrientos, Lorena; Bignon, Alexandre; Gueguen, Claire; Chaisemartin, Luc de; Gorges, Roseline; Sandré, Catherine; Mascarell, Laurent; Balabanian, Karl; Kerdine-Römer, Saadia; Pallardy, Marc; Marin‐Esteban, Viviana; Chollet‐Martin, Sylvie

doi:10.4049/jimmunol.1400586

Cited by 57 publications

(56 citation statements)

References 64 publications

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“…In fact, in agreement with previous studies performed with NET induced by the calcium ionophore A23187 [52] , MSU-induced NET did not induce cytokine secretion by DC, and NET were neither proapoptotic nor cytotoxic for DC (data not shown).…”

Section: Discussionsupporting

confidence: 80%

Neutrophil Extracellular Traps Stimulate Proinflammatory Responses in Human Airway Epithelial Cells

Sabbione¹,

Keitelman²,

Iula³

et al. 2017

J Innate Immun

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Tissue injury leads to the release of uric acid (UA). At high local concentrations, UA can form monosodium urate crystals (MSU). MSU and UA stimulate neutrophils to release extracellular traps (NET). Here, we investigated whether these NET could be involved in the development of inflammation by stimulating cytokine release by airway epithelial cells. We found that NET significantly increased the secretion of CXCL8/IL-8 and IL-6 by alveolar and bronchial epithelial cells. These effects were not observed when NETosis was inhibited by Diphenyleneiodonium, elastase inhibitor, or Cl-amidine. Similar findings were made with NET induced by cigarette smoke extract, suggesting that NET proinflammatory capacity is independent of the inducing stimulus. Furthermore, NET affected neither the viability and morphology of epithelial cells nor the barrier integrity of polarized cells. The epithelial stimulatory capacity of NET was not affected by degradation of DNA with micrococcal nuclease, treatment with heparin, or inhibition of the elastase immobilized to DNA, but it was significantly reduced by pretreatment with an anti-HMGB-1 blocking antibody. Altogether, our findings indicate that NET exert direct proinflammatory effects on airway epithelial cells that might contribute in vivo to the further recruitment of neutrophils and the perpetuation of inflammation upon lung tissue damage.

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Section: Discussionsupporting

confidence: 80%

Neutrophil Extracellular Traps Stimulate Proinflammatory Responses in Human Airway Epithelial Cells

Sabbione¹,

Keitelman²,

Iula³

et al. 2017

J Innate Immun

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“…NETs were prepared as previously described 19. dsDNA in NETs was quantified by Picogreen dsDNA Assay kit (Invitrogen; P7589) according to the manufacturer’s instructions.…”

Section: Methodsmentioning

confidence: 99%

Neutrophil extracellular traps induced by cigarette smoke activate plasmacytoid dendritic cells

Qiu

Zhang

Tang

et al. 2017

Thorax

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“…NETs formed upon activation of neutrophils with Mycobacterium tuberculosis , interact with and activate macrophages, inducing IL-6, tumor necrosis factor-α (TNF-α), IL-1β, and interleukin-10 (IL-10) production (10), and NETs from cholesterol crystal-stimulated neutrophils prime monocytes to produce IL-6 and IL-1β in response to these cholesterol crystal (11). Contrariwise, NETs inhibit the activation of monocyte-derived dendritic cells (mo-DCs) by lipopolysaccharide (LPS) and promote polarization to a Th2 immune response (12). …”

Section: Introductionmentioning

confidence: 99%

Neutrophil Extracellular Traps Reprogram IL-4/GM-CSF-Induced Monocyte Differentiation to Anti-inflammatory Macrophages

et al. 2017

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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.

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Neutrophil Extracellular Traps Downregulate Lipopolysaccharide-Induced Activation of Monocyte-Derived Dendritic Cells

Cited by 57 publications

References 64 publications

Neutrophil Extracellular Traps Stimulate Proinflammatory Responses in Human Airway Epithelial Cells

Neutrophil Extracellular Traps Stimulate Proinflammatory Responses in Human Airway Epithelial Cells

Neutrophil extracellular traps induced by cigarette smoke activate plasmacytoid dendritic cells

Neutrophil Extracellular Traps Reprogram IL-4/GM-CSF-Induced Monocyte Differentiation to Anti-inflammatory Macrophages

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