Extracellular eosinophilic traps in association with Staphylococcus aureus at the site of epithelial barrier defects in patients with severe airway inflammation

Gevaert, Elien; Zhang, Nan; Krysko, Olga; Feng, Lan; Holtappels, Gabriële; Ruyck, Natalie De; Nauwynck, Hans; Yousefi, Shída; Simon, Hans‐Uwe; Bachert, Claus

doi:10.1016/j.jaci.2017.01.019

Cited by 112 publications

(125 citation statements)

References 31 publications

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Section: Eets In Asthma and Rhinosinusitismentioning

confidence: 99%

“…In chronic rhinosinusitis with nasal polyps that is characterized by Th2-biased eosinophilic inflammation, about 8.8% of tissue eosinophils exhibited EETs correlating with IL-5 and periostin tissue levels and colonization with Staphylococcus aureus (S. aureus) 105 . In an ex vivo human mucosal disease tissue model, transepithelial migration at sites of epithelial defects and massive EET formation of eosinophils to entrap S. aureus has been demonstrated 105 . These observations, together with the finding that S. aureus can directly induce EET formation, suggested that, in case of epithelial barrier defects, eosinophils are part of the innate immune response for avoiding the invasion by bacteria 10,105 .…”

Section: Eets In Asthma and Rhinosinusitismentioning

confidence: 99%

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In vivo evidence for extracellular DNA trap formation

et al. 2020

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Extracellular DNA trap formation is a cellular function of neutrophils, eosinophils, and basophils that facilitates the immobilization and killing of invading microorganisms in the extracellular milieu. To form extracellular traps, granulocytes release a scaffold consisting of mitochondrial DNA in association with granule proteins. As we understand more about the molecular mechanism for the formation of extracellular DNA traps, the in vivo function of this phenomenon under pathological conditions remains an enigma. In this article, we critically review the literature to summarize the evidence for extracellular DNA trap formation under in vivo conditions. Extracellular DNA traps have not only been detected in infectious diseases but also in chronic inflammatory diseases, as well as in cancer. While on the one hand, extracellular DNA traps clearly exhibit an important function in host defense, it appears that they can also contribute to the maintenance of inflammation and metastasis, suggesting that they may represent an interesting drug target for such pathological conditions. Facts •The demonstration of extracellular DNA traps in vivo requires sections of affected tissues, which are to be investigated with special staining techniques. These structures are seen in multiple inflammatory and cancer diseases.Is there a simple biomarker that reflects extracellular DNA trap formation?• What is the contribution of extracellular microbe killing compared to intracellular killing following phagocytosis?• The mechanism of DNA trap formation is unknown.

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Section: Eets In Asthma and Rhinosinusitismentioning

confidence: 99%

Section: Eets In Asthma and Rhinosinusitismentioning

confidence: 99%

In vivo evidence for extracellular DNA trap formation

et al. 2020

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“…62,63 Eosinophil-derived DNA traps have recently been implicated in epithelium disruption in CRSwNP. 64 Neutrophils have been suggested to impair epithelial barrier function as well, potentially through releasing oncostatin M, an epithelial barrier disrupting cytokine. 61 IFN-γ was reported to induce activated but insufficient autophagy, leading to p62-dependent apoptosis of nasal epithelial cells in CRSwNP.…”

Section: Epithelial Barrier Defect and Reduced Innate Immunity In Crsmentioning

confidence: 99%

Pathophysiologic mechanisms of chronic rhinosinusitis and their roles in emerging disease endotypes

Cao

Wang

Schleimer

et al. 2019

Annals of Allergy, Asthma & Immunology

102

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Objective: Chronic rhinosinusitis (CRS) is a heterogeneous disorder with distinct pathophysiologic mechanisms. Based on the transcription factor expression and cytokine production patterns in different types of innate lymphoid cells (ILCs), in parallel with those of adaptive CD4+ T helper (Th) cells and CD8+ cytotoxic T (Tc) cells, new perspectives on endotypes of patients are emerging around the immune response deviation into type 1 (orchestrated by ILC1s, Tc1 and Th1 cells), type 2 (characterized by ILC2s, Tc2 and Th2 cells), and type 3 (mediated by ILC3s, Tc17 and Th17 cells) responses. Additionally, cluster analysis has been applied to the endotyping of CRS in recent years, which has provided additional novel insights into the CRS pathogenesis. This article aims to review pathological mechanisms of CRS on the basis of type 1, type 2, and type 3 immune responses and how they inform us to begin to understand CRS endotypes. This article also reviews the recent cluster analysis studies of CRS endotypes. Finally, the impact of endotype on therapeutic management of CRS is summarized. Data Sources: Review of published literature. Study Selections: Relevant literature concerning CRS endotypes and the possible underlying mechanisms were obtained from a PubMed search and summarized here. Results and Conclusion: Both CRSwNP and CRSsNP are comprised of distinct endotypes with distinct deviated immune responses, pathogenic mechanisms, and different responses to medical and surgical treatment. An endotype of CRS with prominent type 2 immune responses is the most well studied endotype, and generally can benefit from treatment with steroids and specific type 2 disrupting biologics.

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“…Eosinophils are involved in host defense and inflammation by phagocytosis of pathogens and secretion of toxic mediators, both functions are central to their role as effector cells. Within the last decade, it has become clear that these cells (just like neutrophils) are able to form extracellular DNA traps that significantly contribute to host defense . However, DNA traps can also contribute to the pathogenesis of chronic infectious, allergic, and autoimmune diseases .…”

Section: Introductionmentioning

confidence: 99%

Oxidative damage of SP-D abolishes control of eosinophil extracellular DNA trap formation

Yousefi

Sharma

Stojkov

et al. 2018

Journal of Leukocyte Biology

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The asthmatic airways are highly susceptible to inflammatory injury by air pollutants such as ozone (O ), characterized by enhanced activation of eosinophilic granulocytes and a failure of immune protective mechanisms. Eosinophil activation during asthma exacerbation contributes to the proinflammatory oxidative stress by high levels of nitric oxide (NO) production and extracellular DNA release. Surfactant protein-D (SP-D), an epithelial cell product of the airways, is a critical immune regulatory molecule with a multimeric structure susceptible to oxidative modifications. Using recombinant proteins and confocal imaging, we demonstrate here that SP-D directly bound to the membrane and inhibited extracellular DNA trap formation by human and murine eosinophils in a concentration and carbohydrate-dependent manner. Combined allergic airway sensitization and O exposure heightened eosinophilia and nos2 mRNA (iNOS) activation in the lung tissue and S-nitrosylation related de-oligomerisation of SP-D in the airways. In vitro reproduction of the iNOS action led to similar effects on SP-D. Importantly, S-nitrosylation abolished the ability of SP-D to block extracellular DNA trap formation. Thus, the homeostatic negative regulatory feedback between SP-D and eosinophils is destroyed by the NO-rich oxidative lung tissue environment in asthma exacerbations.

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Extracellular eosinophilic traps in association with Staphylococcus aureus at the site of epithelial barrier defects in patients with severe airway inflammation

Cited by 112 publications

References 31 publications

In vivo evidence for extracellular DNA trap formation

In vivo evidence for extracellular DNA trap formation

Pathophysiologic mechanisms of chronic rhinosinusitis and their roles in emerging disease endotypes

Oxidative damage of SP-D abolishes control of eosinophil extracellular DNA trap formation

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