Neutrophil extracellular traps: Modulation mechanisms by pathogens

Gonzalez-Contreras, Felipe de Jesus; Zárate, Xristo

doi:10.1016/j.cellimm.2022.104640

Cited by 6 publications

(2 citation statements)

References 163 publications

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“…In some pathologies, such as sepsis and COVID-19, an excess of intravascular NETs damages the endothelium and drives thrombosis, leading to blood flow occlusion and injury of the host tissues ( Zhu et al., 2022a ; Zhu et al., 2022b ). In other infections, the pathogen produces virulence factors to modulate NETs formation or evade their entrapment, such as DNAses, which break down the integrity of the NET-backbone ( Von Köckritz-Blickwede et al., 2016 ; Ríos-López et al., 2021 ; de Jesus Gonzalez-Contreras and Zarate, 2022 ; Janssen et al., 2022 ).…”

Section: Introductionmentioning

confidence: 99%

Clostridium perfringens phospholipase C, an archetypal bacterial virulence factor, induces the formation of extracellular traps by human neutrophils

Badilla-Vargas,

Pereira,

Molina-Mora

et al. 2023

Front. Cell. Infect. Microbiol.

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Neutrophil extracellular traps (NETs) are networks of DNA and various microbicidal proteins released to kill invading microorganisms and prevent their dissemination. However, a NETs excess is detrimental to the host and involved in the pathogenesis of various inflammatory and immunothrombotic diseases. Clostridium perfringens is a widely distributed pathogen associated with several animal and human diseases, that produces many exotoxins, including the phospholipase C (CpPLC), the main virulence factor in gas gangrene. During this disease, CpPLC generates the formation of neutrophil/platelet aggregates within the vasculature, favoring an anaerobic environment for C. perfringens growth. This work demonstrates that CpPLC induces NETosis in human neutrophils. Antibodies against CpPLC completely abrogate the NETosis-inducing activity of recombinant CpPLC and C. perfringens secretome. CpPLC induces suicidal NETosis through a mechanism that requires calcium release from inositol trisphosphate receptor (IP3) sensitive stores, activation of protein kinase C (PKC), and the mitogen-activated protein kinase/extracellular signal-regulated kinase (MEK/ERK) pathways, as well as the production of reactive oxygen species (ROS) by the metabolism of arachidonic acid. Proteomic analysis of the C. perfringens secretome identified 40 proteins, including a DNAse and two 5´-nucleotidases homologous to virulence factors that could be relevant in evading NETs. We suggested that in gas gangrene this pathogen benefits from having access to the metabolic resources of the tissue injured by a dysregulated intravascular NETosis and then escapes and spreads to deeper tissues. Understanding the role of NETs in gas gangrene could help develop novel therapeutic strategies to reduce mortality, improve muscle regeneration, and prevent deleterious patient outcomes.

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Section: Introductionmentioning

confidence: 99%

Clostridium perfringens phospholipase C, an archetypal bacterial virulence factor, induces the formation of extracellular traps by human neutrophils

Badilla-Vargas,

Pereira,

Molina-Mora

et al. 2023

Front. Cell. Infect. Microbiol.

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“…NETs are meshes of chromatin associated with neutrophil proteins released upon the activation of these leukocytes. In the last few decades, it has become clear that NETs function in the containment and elimination of pathogens [ 6 , 7 ], but they can also be deleterious to the host if not well regulated [ 8 , 9 ].…”

Section: Introductionmentioning

confidence: 99%

Leishmania infantum Axenic Amastigotes Induce Human Neutrophil Extracellular Traps and Resist NET-Mediated Killing

Oliveira,

Oliveira-Silva,

Linhares-Lacerda

et al. 2023

TropicalMed

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Neutrophils are multifaceted cells that, upon activation, release meshes of chromatin associated with different proteins, known as neutrophil extracellular traps (NETs). Leishmania amazonensis promastigotes and amastigotes induce NET release, and we have identified the signaling pathways involved in NET extrusion activated by promastigotes. Amastigotes maintain the infection in vertebrate hosts, and we have shown the association of NETs with amastigotes in human biopsies of cutaneous leishmaniasis. However, the interaction of amastigotes and neutrophils remains poorly understood. Our study aimed to characterize the pathways involved in the formation of NETs induced by axenic amastigotes from L. infantum, the causal agent of visceral leishmaniasis. Human neutrophils pretreated with signaling pathway inhibitors were incubated with amastigotes, and NET release was quantified in the culture supernatant. Amastigote viability was checked after incubation with NETs. We found that the release of NETs by neutrophils stimulated with these amastigotes requires the participation of elastase and peptidyl arginine deaminase and the involvement of PI3K, ROS, and calcium. Moreover, amastigotes are not susceptible to NET-mediated killing. Altogether, these findings improve our comprehension of the signaling pathways implicated in the interaction between amastigotes and human neutrophils.

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Unraveling the Molecular Landscape of Neutrophil Extracellular Traps in Severe Asthma: Identification of Biomarkers and Molecular Clusters

Shen,

Lin

2024

Mol Biotechnol

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Neutrophil extracellular traps: Modulation mechanisms by pathogens

Cited by 6 publications

References 163 publications

Clostridium perfringens phospholipase C, an archetypal bacterial virulence factor, induces the formation of extracellular traps by human neutrophils

Clostridium perfringens phospholipase C, an archetypal bacterial virulence factor, induces the formation of extracellular traps by human neutrophils

Leishmania infantum Axenic Amastigotes Induce Human Neutrophil Extracellular Traps and Resist NET-Mediated Killing

Unraveling the Molecular Landscape of Neutrophil Extracellular Traps in Severe Asthma: Identification of Biomarkers and Molecular Clusters

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