The Immune System Throws Its Traps: Cells and Their Extracellular Traps in Disease and Protection

Conceição-Silva, Fátima; Reis, Clarissa Souza Mota; Luca, Paula Mello De; Leite-Silva, Jéssica; Santiago, Marta A; Morrot, Alexandre; Morgado, Fernanda Nazaré

doi:10.3390/cells10081891

Cited by 36 publications

(29 citation statements)

References 205 publications

(435 reference statements)

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“…Fátima Conceição-Silva et al [44] have shown that neutrophils, macrophages, lymphocytes, eosinophils, basophils, and mast cells can produce extracellular traps (ET), even if the modalities are still not completely known. Patients with severe cases of COVID-19 are predisposed to thrombosis in which ETs produced by neutrophils may participate.…”

Section: Basophils and Covid-19 Diseasementioning

confidence: 99%

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Basophils and Mast Cells in COVID-19 Pathogenesis

Murdaca

Gioacchino

Greco³

et al. 2021

Cells

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Basophils and mast cells are among the principal inducers of Th2 responses and have a crucial role in allergic and anti-parasitic protective immunity. Basophils can function as antigen-presenting cells that bind antigens on their surface and boost humoral immune responses, inducing Th2 cell differentiation. Their depletion results in lower humoral memory activation and greater infection susceptibility. Basophils seem to have an active role upon immune response to SARS-CoV-2. In fact, a coordinate adaptive immune response to SARS-CoV-2 is magnified by basophils. It has been observed that basophil amount is lower during acute disease with respect to the recovery phase and that the grade of this depletion is an important determinant of the antibody response to the virus. Moreover, mast cells, present in a great quantity in the nasal epithelial and lung cells, participate in the first immune response to SARS-CoV-2. Their activation results in a hyperinflammatory syndrome through the release of inflammatory molecules, participating to the “cytokine storm” and, in a longer period, inducing pulmonary fibrosis. The literature data suggest that basophil counts may be a useful prognostic tool for COVID-19, since their reduction is associated with a worse prognosis. Mast cells, on the other hand, represent a possible therapeutic target for reducing the airway inflammation characteristic of the hyperacute phase of the disease.

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Section: Basophils and Covid-19 Diseasementioning

confidence: 99%

“…Mast cells are ubiquitous in the body, and they are involved in several conditions including viral infections, systemic inflammatory diseases, asthma, neuroinflammatory diseases, traumatic brain injury, stroke, and several stress disorders [44,56].…”

Section: Basophils and Covid-19 Diseasementioning

confidence: 99%

Basophils and Mast Cells in COVID-19 Pathogenesis

Murdaca

Gioacchino

Greco³

et al. 2021

Cells

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“…Over the last years, many studies linked the process of NETosis to oncogenic transformation, angiogenesis, cancer development and metastasis ( 19 , 20 ). In different pathological contexts (thromboinflammation, atherosclerosis, systemic lupus erythematosus, infection, sepsis), it became also evident that other blood, immune and specialized cells could also generate extracellular traps (ETs) ( 21 , 22 ). In this review, we provide a detailed analysis of extracellular DNA function in cancer and also discuss the different sources and origins of ETs and provide the hypotheses on their possible impact on tumor cells and tumor microenvironment.…”

Section: Introductionmentioning

confidence: 99%

Extracellular DNA Traps: Origin, Function and Implications for Anti-Cancer Therapies

et al. 2022

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Extracellular DNA may serve as marker in liquid biopsies to determine individual diagnosis and prognosis in cancer patients. Cell death or active release from various cell types, including immune cells can result in the release of DNA into the extracellular milieu. Neutrophils are important components of the innate immune system, controlling pathogens through phagocytosis and/or the release of neutrophil extracellular traps (NETs). NETs also promote tumor progression and metastasis, by modulating angiogenesis, anti-tumor immunity, blood clotting and inflammation and providing a supportive niche for metastasizing cancer cells. Besides neutrophils, other immune cells such as eosinophils, dendritic cells, monocytes/macrophages, mast cells, basophils and lymphocytes can also form extracellular traps (ETs) during cancer progression, indicating possible multiple origins of extracellular DNA in cancer. In this review, we summarize the pathomechanisms of ET formation generated by different cell types, and analyze these processes in the context of cancer. We also critically discuss potential ET-inhibiting agents, which may open new therapeutic strategies for cancer prevention and treatment.

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“…In the first scenario, mtDNA is first released into the cytosol, and then is enclosed in vesicles that fuse with the cell membrane, leading to mtDNA extrusion. An alternative possibility is that a fusion of mitochondrial and cell membrane occurs, leading to the release of mitochondrial content, including mtDNA, in the extracellular space [ 100 ].…”

Section: Mechanisms Of Release Of Mtdna In Biological Fluidsmentioning

confidence: 99%

Molecular Mechanisms of mtDNA-Mediated Inflammation

Gaetano

Solodka

Zanini

et al. 2021

Cells

107

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Besides their role in cell metabolism, mitochondria display many other functions. Mitochondrial DNA (mtDNA), the own genome of the organelle, plays an important role in modulating the inflammatory immune response. When released from the mitochondrion to the cytosol, mtDNA is recognized by cGAS, a cGAMP which activates a pathway leading to enhanced expression of type I interferons, and by NLRP3 inflammasome, which promotes the activation of pro-inflammatory cytokines Interleukin-1beta and Interleukin-18. Furthermore, mtDNA can be bound by Toll-like receptor 9 in the endosome and activate a pathway that ultimately leads to the expression of pro-inflammatory cytokines. mtDNA is released in the extracellular space in different forms (free DNA, protein-bound DNA fragments) either as free circulating molecules or encapsulated in extracellular vesicles. In this review, we discussed the latest findings concerning the molecular mechanisms that regulate the release of mtDNA from mitochondria, and the mechanisms that connect mtDNA misplacement to the activation of inflammation in different pathophysiological conditions.

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The Immune System Throws Its Traps: Cells and Their Extracellular Traps in Disease and Protection

Cited by 36 publications

References 205 publications

Basophils and Mast Cells in COVID-19 Pathogenesis

Basophils and Mast Cells in COVID-19 Pathogenesis

Extracellular DNA Traps: Origin, Function and Implications for Anti-Cancer Therapies

Molecular Mechanisms of mtDNA-Mediated Inflammation

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