scholarly journals Toll-Like Receptor 4, but Not Neutrophil Extracellular Traps, Promote IFN Type I Expression to Enhance Th2 Responses to Nippostrongylus brasiliensis

2017 ◽  
Vol 8 ◽  
Author(s):  
Christophe Pellefigues ◽  
Shiau-Choot Tang ◽  
Alfonso Schmidt ◽  
Ruby F. White ◽  
Olivier Lamiable ◽  
...  
Keyword(s):  
Neutrophil Extracellular Traps ◽  
Nippostrongylus Brasiliensis ◽  
Type I ◽  
Toll Like Receptor ◽  
Toll Like Receptor 4 ◽  
Extracellular Traps ◽  
Th2 Responses

scholarly journals Trypanosoma brucei Lipophosphoglycan Induces the Formation of Neutrophil Extracellular Traps and Reactive Oxygen Species Burst via Toll-Like Receptor 2, Toll-Like Receptor 4, and c-Jun N-Terminal Kinase Activation

2021 ◽  
Vol 12 ◽  
Author(s):  
Kai Zhang ◽  
Ning Jiang ◽  
Xiaoyu Sang ◽  
Ying Feng ◽  
Ran Chen ◽  
...  
Keyword(s):  
Reactive Oxygen Species ◽  
Trypanosoma Brucei ◽  
Nicotinamide Adenine Dinucleotide Phosphate ◽  
Reactive Oxygen ◽  
Neutrophil Extracellular Traps ◽  
Oxygen Species ◽  
Toll Like Receptor ◽  
Toll Like Receptor 4 ◽  
Extracellular Traps ◽  
Toll Like Receptor 2

Trypanosoma brucei brucei is the causative agent of African animal trypanosomosis, which mainly parasitizes the blood of the host. Lipophosphoglycan (LPG), a polymer anchored to the surface of the parasites, activates the host immune response. In this study, we revealed that T. brucei LPG stimulated neutrophils to form neutrophil extracellular traps (NETs) and release the reactive oxygen species (ROS). We further analyzed the involvement of toll-like receptor 2 (TLR2) and toll-like receptor 4 (TLR4) and explored the activation of signaling pathway enzymes in response to LPG stimulation. During the stimulation of neutrophils by LPG, the blockade using anti-TLR2 and anti-TLR4 antibodies reduced the phosphorylation of c-Jun N-terminal kinase (JNK), the release of DNA from the NETs, and the burst of ROS. Moreover, the addition of JNK inhibitor and nicotinamide adenine dinucleotide phosphate (NADPH) oxidase inhibitor exhibited similar effects. Our data suggest that T. brucei LPG activates the phosphorylation of JNK through TLR2 and TLR4 recognition, which causes the formation of NETs and the burst of ROS.

scholarly journals Neutrophil Extracellular Traps Are Pathogenic in Ventilator-Induced Lung Injury and Partially Dependent on TLR4

2017 ◽  
Vol 2017 ◽  
pp. 1-13 ◽  
Author(s):  
Haosi Li ◽  
Pinhua Pan ◽  
Xiaoli Su ◽  
Shuai Liu ◽  
Lemeng Zhang ◽  
...  
Keyword(s):  
Lung Injury ◽  
Neutrophil Extracellular Traps ◽  
Toll Like Receptor ◽  
Wild Type ◽  
Toll Like Receptor 4 ◽  
Mechanically Ventilated ◽  
Extracellular Traps ◽  
Ventilator Induced Lung Injury ◽  
Dnase Treatment

The pathogenesis of ventilator-induced lung injury (VILI) is associated with neutrophils. Neutrophils release neutrophil extracellular traps (NETs), which are composed of DNA and granular proteins. However, the role of NETs in VILI remains incompletely understood. Normal saline and deoxyribonuclease (DNase) were used to study the role of NETs in VILI. To further determine the role of Toll-like receptor 4 (TLR4) in NETosis, we evaluated the lung injury and NET formation in TLR4 knockout mice and wild-type mice that were mechanically ventilated. Some measures of lung injury and the NETs markers were significantly increased in the VILI group. DNase treatment markedly reduced NETs markers and lung injury. After high-tidal mechanical ventilation, the NETs markers in the TLR4 KO mice were significantly lower than in the WT mice. These data suggest that NETs are generated in VILI and pathogenic in a mouse model of VILI, and their formation is partially dependent on TLR4.

scholarly journals Human resistin protects against endotoxic shock by blocking LPS–TLR4 interaction

2017 ◽  
Vol 114 (48) ◽  
pp. E10399-E10408 ◽  
Author(s):  
Jessica C. Jang ◽  
Jiang Li ◽  
Luca Gambini ◽  
Hashini M. Batugedara ◽  
Sandeep Sati ◽  
...  
Keyword(s):  
Immune Cell ◽  
Inflammatory Responses ◽  
Endotoxic Shock ◽  
Critical Role ◽  
Nippostrongylus Brasiliensis ◽  
Toll Like Receptor ◽  
Toll Like Receptor 4 ◽  
Therapeutic Function ◽  
Human Immune ◽  
Human Resistin

Helminths trigger multiple immunomodulatory pathways that can protect from sepsis. Human resistin (hRetn) is an immune cell-derived protein that is highly elevated in helminth infection and sepsis. However, the function of hRetn in sepsis, or whether hRetn influences helminth protection against sepsis, is unknown. Employing hRetn-expressing transgenic mice (hRETNTg+) and recombinant hRetn, we identify a therapeutic function for hRetn in lipopolysaccharide (LPS)-induced septic shock. hRetn promoted helminth-induced immunomodulation, with increased survival of Nippostrongylus brasiliensis (Nb)-infected hRETNTg+ mice after a fatal LPS dose compared with naive mice or Nb-infected hRETNTg− mice. Employing immunoprecipitation assays, hRETNTg+Tlr4−/− mice, and human immune cell culture, we demonstrate that hRetn binds the LPS receptor Toll-like receptor 4 (TLR4) through its N terminal and modulates STAT3 and TBK1 signaling, triggering a switch from proinflammatory to anti-inflammatory responses. Further, we generate hRetn N-terminal peptides that are able to block LPS proinflammatory function. Together, our studies identify a critical role for hRetn in blocking LPS function with important clinical significance in helminth-induced immunomodulation and sepsis.

scholarly journals The humoral pattern recognition receptor PTX3 is stored in neutrophil granules and localizes in extracellular traps

2007 ◽  
Vol 204 (4) ◽  
pp. 793-804 ◽  
Author(s):  
Sébastien Jaillon ◽  
Giuseppe Peri ◽  
Yves Delneste ◽  
Isabelle Frémaux ◽  
Andrea Doni ◽  
...  
Keyword(s):  
Innate Immunity ◽  
Neutrophil Extracellular Traps ◽  
Toll Like Receptor ◽  
Myeloid Dendritic Cells ◽  
Opsonic Activity ◽  
Extracellular Traps ◽  
Inflammatory Signals ◽  
Rapid Release ◽  
Specific Granules ◽  
Recognition Receptor

The long pentraxin (PTX) 3 is produced by macrophages and myeloid dendritic cells in response to Toll-like receptor agonists and represents a nonredundant component of humoral innate immunity against selected pathogens. We report that, unexpectedly, PTX3 is stored in specific granules and undergoes release in response to microbial recognition and inflammatory signals. Released PTX3 can partially localize in neutrophil extracellular traps formed by extruded DNA. Eosinophils and basophils do not contain preformed PTX3. PTX3-deficient neutrophils have defective microbial recognition and phagocytosis, and PTX3 is nonredundant for neutrophil-mediated resistance against Aspergillus fumigatus. Thus, neutrophils serve as a reservoir, ready for rapid release, of the long PTX3, a key component of humoral innate immunity with opsonic activity.

scholarly journals Neutrophil extracellular traps promote tPA-induced brain hemorrhage via cGAS in mice with stroke

Blood ◽  
2021 ◽  
Author(s):  
Ranran Wang ◽  
Yuanbo Zhu ◽  
Zhongwang Liu ◽  
Luping Chang ◽  
Xiaofei Bai ◽  
...  
Keyword(s):  
Ischemic Stroke ◽  
Thrombolytic Therapy ◽  
Clinical Problem ◽  
Neutrophil Extracellular Traps ◽  
Artery Occlusion ◽  
Type I ◽  
Brain Hemorrhage ◽  
Extracellular Traps ◽  
Dnase 1

Intracerebral hemorrhage associated with thrombolytic therapy with tissue plasminogen activator (tPA) in acute ischemic stroke continues to present a major clinical problem. Here, we report that infusion of tPA resulted in a significant increase in markers of neutrophil extracellular traps (NETs) in the ischemic cortex and plasma of mice subjected to photothrombotic middle cerebral artery occlusion. Peptidylarginine deiminase 4 (PAD4), a critical enzyme for NET formation, is also significantly upregulated in the ischemic brains in tPA-treated mice. Blood-brain barrier (BBB) disruption following ischemic challenge in an in vitro model of BBB was exacerbated after exposure to NETs. Importantly, disruption of NETs by DNase 1 or inhibition of NET production by PAD4 deficiency restored tPA-induced loss of BBB integrity and consequently decreased tPA-associated brain hemorrhage after ischemic stroke. Furthermore, either DNase 1 or PAD4 deficiency reversed tPA-mediated upregulation of the DNA sensor cyclic GMP-AMP (cGAMP) synthase (cGAS). Administration of cGAMP after stroke abolished DNase 1-mediated downregulation of the STING pathway and type I interferon (IFN) production, and blocked the antihemorrhagic effect of DNase 1 in tPA-treated mice. We also show that tPA-associated brain hemorrhage after ischemic stroke was significantly reduced in cGas-/- mice. Collectively, these findings demonstrate that NETs significantly contribute to tPA-induced BBB breakdown in ischemic brain, and suggest that targeting NETs or cGAS may ameliorate thrombolytic therapy for ischemic stroke by reducing tPA-associated hemorrhage.

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