Toxoplasma gondii-Induced Neutrophil Extracellular Traps Amplify the Innate and Adaptive Response

Miranda, Farlen José Bebber; Rocha, Bruno Coelho; Pereira, Milton; Pereira, Larissa M. N.; Souza, Erikson H. M. de; Marino, Ana Paula M.P.; Costa, P.A.C.R.; Vasconcelos-Santos, Daniel Vítor; Antonelli, Lis R. V.; Gazzinelli, Ricardo T.

doi:10.1128/mbio.01307-21

Cited by 25 publications

(23 citation statements)

References 51 publications

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“…For another, sPTB is inseparable from the function of inflammatory factors 36,37 . Some studies have reported that NETs can modulate the secretion of inflammatory factors 38–40 . Our results showed that NETs can remarkably upregulate the expression of pro‐inflammatory factors (IL‐6, IL‐8, IL‐1β, and TNF‐α) and promote the secretion of IL‐6 and IL‐8 in hAECs.…”

Section: Resultsmentioning

confidence: 54%

“…36,37 Some studies have reported that NETs can modulate the secretion of inflammatory factors. [38][39][40] Our results showed that NETs can remarkably upregulate the expression of pro-inflammatory factors (IL-6, IL-8, IL-1β, and TNF-α) and promote the secretion of IL-6 and IL-8 in hAECs. Therefore, we can speculate that NETs can promote the production of IL-6, IL-8, IL-1β, and TNF-α, which may increase the probability of sPTB.…”

Section: Nets Induce Inflammation In Haecsmentioning

confidence: 63%

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NETs promote ROS production to induce human amniotic epithelial cell apoptosis via ERK1/2 signaling in spontaneous preterm birth

et al. 2022

American J Rep Immunol

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Problem: Premature birth is a common obstetric complication but its pathogenesis is unclear. Inflammation at the maternal-fetal interface in preterm labor leads to the infiltration of neutrophils, which promotes inflammatory responses and induces the degradation of extracellular matrix and cell apoptosis, thus contributing to preterm labor. It is unclear whether neutrophil extracellular traps (NETs), a functional form of neutrophils, are involved in preterm labor. Methods of Study: After collecting amniotic membranes from research objects, we localized NETs by immunofluorescence and evaluated the expression of matrix metalloproteinase (MMP)-9 and MMP-2 by western blotting. Primary human amniotic epithelial cells (hAECs) subjected to treatment with NETs, 5-ethynyl-20-deoxyuridine cell proliferation assay, lactate dehydrogenase (LDH) assay, western blotting, and flow cytometry apoptosis assay were used to determine the effects of NETs on hAECs. We also elucidated possible mechanisms underlying the effects. Results: Compared with normal term women, NETs infiltration and MMP-9 expression in the amniotic membrane from preterm women had increased. Thereafter, NETs might suppress the proliferation and promote the apoptosis of hAECs. Furthermore, after NETs treatment, the mitochondrial membrane potential was significantly decreased, ERK1/2 phosphorylation expression was upregulated and reactive oxygen species (ROS) production was increased in hAECs. Changes in cell proliferation, LDH release, and cell apoptosis level due to NETs could be reversed by ROS inhibitor or ERK phosphorylation inhibitors. Conclusions: NETs can promote the apoptosis of hAECs via ERK1/2 pathways dependent on ROS release.

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Section: Resultsmentioning

confidence: 54%

Section: Nets Induce Inflammation In Haecsmentioning

confidence: 63%

NETs promote ROS production to induce human amniotic epithelial cell apoptosis via ERK1/2 signaling in spontaneous preterm birth

et al. 2022

American J Rep Immunol

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“…This suggests that glycolytic ATP plays an important role in the formation of NETs (34). Additionally, dimethyl malonate acts as a neutrophil succinate dehydrogenase inhibitor and reduces NETs release (35). These results suggest that glycolysis may be involved in NET formation through various biological mechanisms.…”

Section: Role Of Glycolysis In Innate Immune Cellsmentioning

confidence: 86%

Glycolysis in Innate Immune Cells Contributes to Autoimmunity

Chen

Zhang

et al. 2022

Front. Immunol.

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Autoimmune diseases (AIDs) refer to connective tissue inflammation caused by aberrant autoantibodies resulting from dysfunctional immune surveillance. Most of the current treatments for AIDs use non-selective immunosuppressive agents. Although these therapies successfully control the disease process, patients experience significant side effects, particularly an increased risk of infection. There is a great need to study the pathogenesis of AIDs to facilitate the development of selective inhibitors for inflammatory signaling to overcome the limitations of traditional therapies. Immune cells alter their predominant metabolic profile from mitochondrial respiration to glycolysis in AIDs. This metabolic reprogramming, known to occur in adaptive immune cells, i.e., B and T lymphocytes, is critical to the pathogenesis of connective tissue inflammation. At the cellular level, this metabolic switch involves multiple signaling molecules, including serine–threonine protein kinase, mammalian target of rapamycin, and phosphoinositide 3-kinase. Although glycolysis is less efficient than mitochondrial respiration in terms of ATP production, immune cells can promote disease progression by enhancing glycolysis to satisfy cellular functions. Recent studies have shown that active glycolytic metabolism may also account for the cellular physiology of innate immune cells in AIDs. However, the mechanism by which glycolysis affects innate immunity and participates in the pathogenesis of AIDs remains to be elucidated. Therefore, we reviewed the molecular mechanisms, including key enzymes, signaling pathways, and inflammatory factors, that could explain the relationship between glycolysis and the pro-inflammatory phenotype of innate immune cells such as neutrophils, macrophages, and dendritic cells. Additionally, we summarize the impact of glycolysis on the pathophysiological processes of AIDs, including systemic lupus erythematosus, rheumatoid arthritis, vasculitis, and ankylosing spondylitis, and discuss potential therapeutic targets. The discovery that immune cell metabolism characterized by glycolysis may regulate inflammation broadens the avenues for treating AIDs by modulating immune cell metabolism.

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“…IL-17A acts as a pro-inflammatory factor that promotes PF by depending on NETs [51,87]. Furthermore, NETs also promote the release of cytokines such as IL-1, TNF-α, IL-1RA and IL-1α [51,88,89]. The essential role of NETs-produced inflammatory factors is clearly important in PF progression.…”

Section: Nets-mediated Inflammation and Pulmonary Fibrosismentioning

confidence: 99%

Neutrophil extracellular traps and pulmonary fibrosis: an update

Yan

Liu

et al. 2023

J Inflamm

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Pulmonary fibrosis (PF) is a serious and often fatal illness that occurs in various clinical settings and represents a significant unmet medical need. Increasing evidence indicates that neutrophil extracellular traps (NETs) contribute significantly to the progression of PF. Therefore, understanding the pathways by which NETs contribute to the disease is crucial for developing effective treatments. This review focuses on the formation of NETs and the common mechanisms of NETs in PF.

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Toxoplasma gondii-Induced Neutrophil Extracellular Traps Amplify the Innate and Adaptive Response

Abstract: Approximately one-third of the human population is estimated to be chronically infected with the obligate intracellular parasite Toxoplasma gondii . Humans are accidental hosts that are infected with T. gondii after consumption of undercooked meat or contaminated water.

Cited by 25 publications

References 51 publications

NETs promote ROS production to induce human amniotic epithelial cell apoptosis via ERK1/2 signaling in spontaneous preterm birth

NETs promote ROS production to induce human amniotic epithelial cell apoptosis via ERK1/2 signaling in spontaneous preterm birth

Glycolysis in Innate Immune Cells Contributes to Autoimmunity

Neutrophil extracellular traps and pulmonary fibrosis: an update

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