Macrophage Clearance of Neutrophil Extracellular Traps Is a Silent Process

Farrera, Consol; Fadeel, Bengt

doi:10.4049/jimmunol.1300436

Cited by 341 publications

(329 citation statements)

References 43 publications

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“…Also, in our experiments, we observed that IgA-induced NETs were able to ensnare live bacteria, but bacterial viability was not diminished (data not shown). As such, it is possible that, in addition to direct cytotoxic effects, NETs also function to contain bacteria for removal by other immune cells like macrophage (42,43). In fact, dying of PMNs through NETosis may have a second function besides the release of NETs.…”

Section: Discussionmentioning

confidence: 99%

IgA Enhances NETosis and Release of Neutrophil Extracellular Traps by Polymorphonuclear Cells via Fcα Receptor I

Aleyd

Hout

Ganzevles

et al. 2014

The Journal of Immunology

105

101

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Polymorphonuclear cells (neutrophils) are the first cells that arrive at sites of infections. According to the current dogma, they are involved in eliminating bacteria, after which they die through apoptosis. We now demonstrate that enhanced IgA-induced phagocytosis of bacteria or beads by neutrophils led to increased cell death. Nuclear changes and positivity for the general cell death marker 7-aminoactinomycin D were observed, but the absence of annexin V membrane staining supported that neutrophils did not die via apoptosis, in contrast to neutrophils that had not phagocytosed bacteria. Moreover, increased release of neutrophil extracellular traps (NETs) was observed, which was most likely due to augmented production of reactive oxygen species after uptake of IgA-opsonized particles. Blocking the IgA Fc receptor FcαRI abrogated phagocytosis and NET formation. Thus, FcαRI triggering on neutrophils resulted in a rapid form of cell death that is referred to as NETosis, as it is accompanied by the release of NETs. As such, IgA may play a prominent role in mucosal inflammatory responses, where it is the most prominent Ab, because it enhanced both phagocytosis of bacteria and formation of NETs, which are effective mechanisms that neutrophils employ to eliminate pathogens.

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Section: Discussionmentioning

confidence: 99%

IgA Enhances NETosis and Release of Neutrophil Extracellular Traps by Polymorphonuclear Cells via Fcα Receptor I

Aleyd

Hout

Ganzevles

et al. 2014

The Journal of Immunology

105

101

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“…In particular, PMN can control DC activation via several mechanisms [reviewed in (26,27)]. The effects of NETs on APC maturation are unclear (21,(42)(43)(44). We thus took advantage of our previously described method for preparing and quantifying isolated functional NETs (5) to study the impact of calibrated NETs on moDC maturation and its functional consequences.…”

Section: Discussionmentioning

confidence: 99%

“…These reports tend to support a proinflammatory effect of NETs on APCs. However, an in vitro study showed no proinflammatory effect of NETs alone on macrophages (44), and aggregated NETs promote the resolution of inflammation in a murine gout model (45). The conflicting effects reported in the literature might be related to technical variations in NET preparation and APC models.…”

mentioning

confidence: 99%

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

Barrientos

Bignon

Gueguen

et al. 2014

The Journal of Immunology

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Polymorphonuclear neutrophils (PMN) play a central role in inflammation and participate in its control, notably by modulating dendritic cell (DC) functions via soluble mediators or cell–cell contacts. Neutrophil extracellular traps (NETs) released by PMN could play a role in this context. To evaluate NET effects on DC maturation, we developed a model based on monocyte-derived DC (moDC) and calibrated NETs isolated from fresh human PMN. We found that isolated NETs alone had no discernable effect on moDC. In contrast, they downregulated LPS-induced moDC maturation, as shown by decreased surface expression of HLA-DR, CD80, CD83, and CD86, and by downregulated cytokine production (TNF-α, IL-6, IL-12, IL-23), with no increase in the expression of tolerogenic DC genes. Moreover, the presence of NETs during moDC maturation diminished the capacity of these moDC to induce T lymphocyte proliferation in both autologous and allogeneic conditions, and modulated CD4+ T lymphocyte polarization by promoting the production of Th2 cytokines (IL-5 and IL-13) and reducing that of Th1 and Th17 cytokines (IFN-γ and IL-17). Interestingly, the expression and activities of the lymphoid chemokine receptors CCR7 and CXCR4 on moDC were not altered when moDC matured in the presence of NETs. Together, these findings reveal a new role for NETs in adaptive immune responses, modulating some moDC functions and thereby participating in the control of inflammation.

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“…La rupture conjointe des membranes nucléaire et granulaire conduit au mélange des composants cytoplasmiques, granulaires et nucléaires, puis la rupture de la membrane plasmique permet la libération des NET dans l'espace extracellulaire (Figure 2). Afin de maintenir l'homéostasie, les NET sont ensuite dégradés par l'action conjointe de la DNase 1 et d'un mécanisme d'endocytose impliquant les macrophages [4]. En parallèle de ce modèle « classique », plusieurs études ont rapporté un phénomène de nétose rapide (5-60 min) dans différents modèles expérimentaux [5][6][7].…”

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