scholarly journals The Role of DNA in the Extracellular Environment: A Focus on NETs, RETs and Biofilms

2020 ◽  
Vol 11 ◽  
Author(s):  
Francesco Monticolo ◽  
Emanuela Palomba ◽  
Pasquale Termolino ◽  
Pasquale Chiaiese ◽  
Elisabetta de Alteriis ◽  
...  
Keyword(s):  
Genetic Material ◽  
Active Role ◽  
Protective Role ◽  
Extracellular Dna ◽  
Extracellular Matrices ◽  
Pathogen Invasion ◽  
Extracellular Traps ◽  
Molecular Pattern ◽  
Extracellular Environment

The capacity to actively release genetic material into the extracellular environment has been reported for bacteria, archaea, fungi, and in general, for microbial communities, but it is also described in the context of multicellular organisms, animals and plants. This material is often present in matrices that locate outside the cells. Extracellular matrices have important roles in defense response and disease in microbes, animal and plants cells, appearing as barrier against pathogen invasion or for their recognition. Specifically, neutrophils extracellular traps (NETs) in animals and root extracellular traps (RETs) in plants, are recognized to be important players in immunity. A growing amount of evidence revealed that the extracellular DNA, in these contexts, plays an active role in the defense action. Moreover, the protective role of extracellular DNA against antimicrobials and mechanical stress also appears to be confirmed in bacterial biofilms. In parallel, recent efforts highlighted different roles of self (homologous) and non-self (heterologous) extracellular DNA, paving the way to discussions on its role as a “Damage-associated molecular pattern” (DAMP). We here provide an evolutionary overview on extracellular DNA in extracellular matrices like RETs, NETs, and microbial biofilms, discussing on its roles and inferring on possible novel functionalities.

scholarly journals Precancerous niche (PCN), a product of fibrosis with remodeling by incessant chronic inflammation

4open ◽  
2019 ◽  
Vol 2 ◽  
pp. 11 ◽  
Author(s):  
Björn L.D.M. Brücher ◽  
Ijaz S. Jamall
Keyword(s):  
Extracellular Matrix ◽  
Chronic Inflammation ◽  
Genetic Material ◽  
Cell Communication ◽  
Cell Types ◽  
Complex Signaling ◽  
Different Cell Types ◽  
Multiple Signaling ◽  
Extracellular Environment

Fibroblasts are actively involved in the creation of the stroma and the extracellular matrix which are important for cell adhesion, cell–cell communication, and tissue metabolism. The role of fibrosis in carcinogenesis can be examined by analogy to tissues of various cancers. The orchestration of letters in the interplay of manifold components with signaling and crosstalk is incompletely understood but available evidence suggests a hitherto underappreciated role for fibrosis in carcinogenesis. Complex signaling and crosstalk by pathogenic stimuli evoke persistent subclinical inflammation, which in turn, results in a cascade of different cell types, ubiquitous proteins and their corresponding enzymes, cytokine releases, and multiple signaling pathways promoting the onset of fibrosis. There is considerable evidence that the body's attempt to resolve such a modified extracellular environment leads to further disruption of homeostasis and the genesis of the precancerous niche as part of the six-step process that describes carcinogenesis. The precancerous niche is formed and can be understood to develop as a result of (1) pathogenic stimulus, (2) chronic inflammation, and (3) fibrosis with alterations of the extracellular matrix, stromal rigidity, and mechano-transduction. This is why carcinogenesis is not just a process of aberrant cell growth with damaged genetic material but the role of the PCN in its entirety reveals how carcinogenesis can occur without invoking the need for somatic mutations.

scholarly journals Neutrophil-Extracellular Traps, Cell-Free DNA, and Immunothrombosis in Companion Animals: A Review

2019 ◽  
Vol 57 (1) ◽  
pp. 6-23 ◽  
Author(s):  
Robert Goggs ◽  
Unity Jeffery ◽  
Dana N. LeVine ◽  
Ronald H. L. Li
Keyword(s):  
Companion Animals ◽  
High Mobility ◽  
Extracellular Dna ◽  
Death Process ◽  
Cell Free Dna ◽  
Pathogen Invasion ◽  
Extracellular Traps ◽  
Trap Formation ◽  
Free Dna ◽  
Extracellular Trap

Immunothrombosis is a potentially beneficial physiological process that aids innate immunity and host defense against pathogen invasion. However, this process can also be damaging when it occurs to excess or in critical blood vessels. Formation of extracellular traps by leukocytes, particularly neutrophils, is central to our understanding of immunothrombosis. In addition to degranulation and phagocytosis, extracellular traps are the third mechanism by which neutrophils combat potential pathogens. These traps consist of extracellular DNA decorated with bactericidal cellular proteins, including elastase, myeloperoxidase, and cathepsins. Neutrophils can release these structures as part of a controlled cell-death process or via a process termed vital NETosis that enables the cells to extrude DNA but remain viable. There is accumulating evidence that NETosis occurs in companion animals, including dogs, horses, and cats, and that it actively contributes to pathogenesis. Numerous studies have been published detailing various methods for identification and quantification of extracellular trap formation, including cell-free DNA, measurements of histones and proteins such as high-mobility group box–1, and techniques involving microscopy and flow cytometry. Here, we outline the present understanding of these phenomena and the mechanisms of extracellular trap formation. We critically review the data regarding measurement of NETosis in companion animals, summarize the existing literature on NETosis in veterinary species, and speculate on what therapeutic options these insights might present to clinicians in the future.

Proinflammatory role of neutrophil extracellular traps in abdominal sepsis

2014 ◽  
Vol 307 (7) ◽  
pp. L586-L596 ◽  
Author(s):  
Lingtao Luo ◽  
Su Zhang ◽  
Yongzhi Wang ◽  
Milladur Rahman ◽  
Ingvar Syk ◽  
...  
Keyword(s):  
Lung Injury ◽  
Peritoneal Cavity ◽  
Tissue Injury ◽  
Cecal Ligation ◽  
Neutrophil Extracellular Traps ◽  
Abdominal Sepsis ◽  
Extracellular Dna ◽  
Extracellular Traps ◽  
Proinflammatory Role

Excessive neutrophil activation is a major component in septic lung injury. Neutrophil-derived DNA may form extracellular traps in response to bacterial invasions. The aim of the present study was to investigate the potential role of neutrophil extracellular traps (NETs) in septic lung injury. Male C57BL/6 mice were treated with recombinant human (rh)DNAse (5 mg/kg) after cecal ligation and puncture (CLP). Extracellular DNA was stained by Sytox green, and NET formation was quantified by confocal microscopy and cell-free DNA in plasma, peritoneal cavity, and lung. Blood, peritoneal fluid, and lung tissue were harvested for analysis of neutrophil infiltration, NET levels, tissue injury, as well as CXC chemokine and cytokine formation. We observed that CLP caused increased formation of NETs in plasma, peritoneal cavity, and lung. Administration of rhDNAse not only eliminated NET formation in plasma, peritoneal cavity, and bronchoalveolar space but also reduced lung edema and tissue damage 24 h after CLP induction. Moreover, treatment with rhDNAse decreased CLP-induced formation of CXC chemokines, IL-6, and high-mobility group box 1 (HMGB1) in plasma, as well as CXC chemokines and IL-6 in the lung. In vitro, we found that neutrophil-derived NETs had the capacity to stimulate secretion of CXCL2, TNF-α, and HMGB1 from alveolar macrophages. Taken together, our findings show that NETs regulate pulmonary infiltration of neutrophils and tissue injury via formation of proinflammatory compounds in abdominal sepsis. Thus we conclude that NETs exert a proinflammatory role in septic lung injury.

scholarly journals Callose formation in injured cells of the vegetative and generative thallus of Chara vulgaris L. Absence of callose in the process of cytodifferentiation

2014 ◽  
Vol 57 (1) ◽  
pp. 21-30 ◽  
Author(s):  
Mirosław Godlewski
Keyword(s):  
Water Potential ◽  
Protective Role ◽  
Sudden Increase ◽  
Callose Deposition ◽  
Chara Vulgaris ◽  
Callose Formation ◽  
Extracellular Environment ◽  
Vegetative System ◽  
Generative Organs

In an alga <em>Chara vulgaris</em> L. the processes of differentiation of vegetative system cells of the thallus, and initiation and development of generative organs are not associated with callose formation. It was demonstrated that damage to any of the somatic cells and also generative and nongenerative cells of the antheridium and oogonium are capable of callose formation independently of their developmental stage. The localisation and thickness of these layers depend on the way the cells are injured and on their size. The protective role of callose in such cells may consist, beside strengthening the damaged walls, in protection of the symplast by formation of callose deposits on the walls with plasmodesmata; it may also consist in increasing the water potential of the cells. Experiments in which callose deposition was provoked by pressing of the cells or damage leading to a sudden increase of the water potential of the extracellular environment suggest that a sudden increase of tension in the cells may be a factor triggering the "callose effect".

scholarly journals SOCE-inhibitor reduced human sperm-induced formation of neutrophil extracellular traps

Reproduction ◽  
2021 ◽  
Vol 161 (1) ◽  
pp. 21-29
Author(s):  
Fabiola Zambrano ◽  
Liliana Silva ◽  
Pamela Uribe ◽  
Ulrich Gärtner ◽  
Anja Taubert ◽  
...  
Keyword(s):  
Binding Capacity ◽  
Human Sperm ◽  
Neutrophil Extracellular Traps ◽  
Positive Control ◽  
Polymorphonuclear Neutrophils ◽  
Extracellular Dna ◽  
Dna Integrity ◽  
Extracellular Traps

Human spermatozoa activate neutrophil extracellular traps (NETs) in vitro. NETosis is an efficient mechanism through which polymorphonuclear neutrophils (PMN) capture sperm in vitro. The objective of this study was to establish the role of store-operated Ca+2 entry (SOCE) in human sperm-triggered NETs and its impact on sperm integrity and oocyte binding capacity. PMN isolated from donors were exposed to spermatozoa isolated from normozoospermic donors using the swim-up technique and were divided into the following groups: (1) sperm, (2) PMN, (3) PMN + sperm, (4) PMN (pretreated with 2-APB, SOCE inhibitor) + sperm, (5) (PMN + DNase) + sperm, and (6) (PMN + PMA) + sperm (positive control). NETs were quantified using PicoGreen® and visualised by scanning electron microscopy and immunofluorescence of extracellular DNA and neutrophil elastase. Plasma membrane, acrosome, and DNA integrity were analysed by flow cytometry, and oocyte binding was evaluated using the hemizona pellucida assay. Sperm-triggered NETosis negatively affected the sperm membrane and acrosome integrity and decreased the oocyte binding capacity. These effects were negated by an SOCE inhibitor, thus improving sperm function and achieving high oocyte binding capacity. The SOCE inhibitor significantly reduced NET formation compared with that in control PMN/sperm (P < 0.05). Collectively, these results advance the knowledge about the role of PMN in reproduction and will allow the development of strategies to block NET formation in situations of reduced fertilisation success.

scholarly journals Role of S100A8/A9 for Cytokine Secretion, Revealed in Neutrophils Derived from ER-Hoxb8 Progenitors

2021 ◽  
Vol 22 (16) ◽  
pp. 8845
Author(s):  
Yang Zhou ◽  
Justine Hann ◽  
Véronique Schenten ◽  
Sébastien Plançon ◽  
Jean-Luc Bueb ◽  
...  
Keyword(s):  
Nuclear Factor Kappa B ◽  
Nicotinamide Adenine Dinucleotide Phosphate ◽  
Inflammatory Cells ◽  
Cytokine Secretion ◽  
Suitable Model ◽  
Wild Type ◽  
Molecular Pattern ◽  
Extracellular Environment ◽  
Nadph Oxidase Activation

S100A9, a Ca2+-binding protein, is tightly associated to neutrophil pro-inflammatory functions when forming a heterodimer with its S100A8 partner. Upon secretion into the extracellular environment, these proteins behave like damage-associated molecular pattern molecules, which actively participate in the amplification of the inflammation process by recruitment and activation of pro-inflammatory cells. Intracellular functions have also been attributed to the S100A8/A9 complex, notably its ability to regulate nicotinamide adenine dinucleotide phosphate (NADPH) oxidase activation. However, the complete functional spectrum of S100A8/A9 at the intracellular level is far from being understood. In this context, we here investigated the possibility that the absence of intracellular S100A8/A9 is involved in cytokine secretion. To overcome the difficulty of genetically modifying neutrophils, we used murine neutrophils derived from wild-type and S100A9−/− Hoxb8 immortalized myeloid progenitors. After confirming that differentiated Hoxb8 neutrophil-like cells are a suitable model to study neutrophil functions, our data show that absence of S100A8/A9 led to a dysregulation of cytokine secretion after lipopolysaccharide (LPS) stimulation. Furthermore, we demonstrate that S100A8/A9-induced cytokine secretion was regulated by the nuclear factor kappa B (NF-κB) pathway. These results were confirmed in human differentiated HL-60 cells, in which S100A9 was inhibited by shRNAs. Finally, our results indicate that the degranulation process could be involved in the regulation of cytokine secretion by S100A8/A9.

scholarly journals The Emerging Role of Small Extracellular Vesicles in Inflammatory Airway Diseases

Diagnostics ◽  
2021 ◽  
Vol 11 (2) ◽  
pp. 222
Author(s):  
Katarzyna Piszczatowska ◽  
Katarzyna Czerwaty ◽  
Anna M. Cyran ◽  
Mathias Fiedler ◽  
Nils Ludwig ◽  
...  
Keyword(s):  
Extracellular Vesicles ◽  
Genetic Material ◽  
Upper Airway ◽  
Chronic Obstructive ◽  
Obstructive Pulmonary Disease ◽  
Pathogen Invasion ◽  
Airway Diseases ◽  
Airway Infections ◽  
Inflammatory Processes

Extracellular vesicles (EVs) are produced and released by all cells and are present in all body fluids. They exist in a variety of sizes, however, small extracellular vesicles (sEVs), the EV subset with a size range from 30 to 150 nm, are of current interest. By transporting a complex cargo that includes genetic material, proteins, lipids, and signaling molecules, sEVs can alter the state of recipient cells. The role of sEVs in mediating inflammatory processes and responses of the immune system is well-documented, and adds another layer of complexity to our understanding of frequent diseases, including chronic rhinosinusitis (CRS), asthma, chronic obstructive pulmonary disease (COPD), and upper airway infections. In these diseases, two aspects of sEV biology are of particular interest: (1) sEVs might be involved in the etiopathogenesis of inflammatory airway diseases, and might emerge as attractive therapeutic targets, and (2) sEVs might be of diagnostic or prognostic relevance. The purpose of this review is to outline the biological functions of sEVs and their capacity to both augment and attenuate inflammation and immune response in the context of pathogen invasion, CRS, asthma, and COPD.

scholarly journals DNA secretion and gene-level selection in bacteria

Microbiology ◽  
2006 ◽  
Vol 152 (9) ◽  
pp. 2683-2688 ◽  
Author(s):  
Jeremy A. Draghi ◽  
Paul E. Turner
Keyword(s):  
Mathematical Model ◽  
Population Genetics ◽  
Genetic Material ◽  
Extracellular Dna ◽  
Bacterial Cells ◽  
Gene Level ◽  
Natural Genetic Transformation ◽  
Dna Pool ◽  
Extracellular Environment ◽  
Living Bacteria

Natural genetic transformation can facilitate gene transfer in many genera of bacteria and requires the presence of extracellular DNA. Although cell lysis can contribute to this extracellular DNA pool, several studies have suggested that the secretion of DNA from living bacteria may also provide genetic material for transformation. This paper reviews the evidence for specific secretion of DNA from intact bacteria into the extracellular environment and examines this behaviour from a population-genetics perspective. A mathematical model demonstrates that the joint action of DNA secretion and transformation creates a novel type of gene-level natural selection. This model demonstrates that gene-level selection could explain the existence of DNA secretion mechanisms that provide no benefit to individual cells or populations of bacteria. Additionally, the model predicts that any trait affecting DNA secretion will experience selection at the gene level in a transforming population. This analysis confirms that the secretion of DNA from intact bacterial cells is fully explicable with evolutionary theory, and reveals a novel mechanism for bacterial evolution.

scholarly journals Immunity to Sda1 Protects against Infection by Sda1+ and Sda1− Serotypes of Group A Streptococcus

Vaccines ◽  
2022 ◽  
Vol 10 (1) ◽  
pp. 102
Author(s):  
Shuai Bi ◽  
Jie Wang ◽  
Meiyi Xu ◽  
Ning Li ◽  
Beinan Wang
Keyword(s):  
Protective Immunity ◽  
Vaccine Candidate ◽  
Group A Streptococcus ◽  
Protective Role ◽  
Gas Reservoir ◽  
Extracellular Traps ◽  
Mucosal Site ◽  
Group A ◽  
Potential Vaccine

Group A Streptococcus (GAS) causes a variety of diseases globally. The DNases in GAS promote GAS evasion of neutrophil killing by degrading neutrophil extracellular traps (NETs). Sda1 is a prophage-encoded DNase associated with virulent GAS strains. However, protective immunity against Sda1 has not been determined. In this study, we explored the potential of Sda1 as a vaccine candidate. Sda1 was used as a vaccine to immunize mice intranasally. The effect of anti-Sda1 IgG in neutralizing degradation of NETs was determined and the protective role of Sda1 was investigated with intranasal and systemic challenge models. Antigen-specific antibodies were induced in the sera and pharyngeal mucosal site after Sda1 immunization. The anti-Sda1 IgG efficiently prevented degradation of NETs by supernatant samples from different GAS serotypes with or without Sda1. Sda1 immunization promoted clearance of GAS from the nasopharynx independent of GAS serotypes but did not reduce lethality after systemic GAS challenge. Anti-Sda1 antibody can neutralize degradation of NETs by Sda1 and other phage-encoded DNases and decrease GAS colonization at the nasopharynx across serotypes. These results indicate that Sda1 can be a potential vaccine candidate for reduction in GAS reservoir and GAS tonsillitis-associated diseases.

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