Interferon-γ (IFN-γ) Contributes to the Formation of Neutrophil Extracellular Traps (NETs) for Host Defense AgainstS. pneumoniaeduring Pneumonia.

Sterile Inflammation ◽

Extracellular Traps ◽

Health And Disease

Neutrophils are first responders of antimicrobial host defense and sterile inflammation, and therefore, play important roles during health and disease [...]

Glutathione Reductase Facilitates Host Defense by Sustaining Phagocytic Oxidative Burst and Promoting the Development of Neutrophil Extracellular Traps

The Journal of Immunology ◽

10.4049/jimmunol.1102683 ◽

2012 ◽

Vol 188 (5) ◽

pp. 2316-2327 ◽

Cited By ~ 46

Author(s):

Jing Yan ◽

Xiaomei Meng ◽

Lyn M. Wancket ◽

Katherine Lintner ◽

Leif D. Nelin ◽

...

Keyword(s):

Glutathione Reductase ◽

Host Defense ◽

Oxidative Burst ◽

Neutrophil extracellular traps in the host defense against sepsis induced by Burkholderia pseudomallei (melioidosis)

Intensive Care Medicine Experimental ◽

10.1186/s40635-014-0021-2 ◽

2014 ◽

Vol 2 (1) ◽

Cited By ~ 16

Author(s):

Hanna K de Jong ◽

Gavin CKW Koh ◽

Ahmed Achouiti ◽

Anne J van der Meer ◽

Ingrid Bulder ◽

...

Keyword(s):

Host Defense ◽

Burkholderia Pseudomallei ◽

Neutrophil Extracellular Traps in the Amniotic Cavity of Women with Intra-Amniotic Infection: A New Mechanism of Host Defense

Reproductive Sciences ◽

10.1177/1933719116678690 ◽

2016 ◽

Vol 24 (8) ◽

pp. 1139-1153 ◽

Cited By ~ 31

Author(s):

Nardhy Gomez-Lopez ◽

Roberto Romero ◽

Yi Xu ◽

Derek Miller ◽

Ronald Unkel ◽

...

Keyword(s):

Host Defense ◽

Amniotic Cavity ◽

Neutrophil Extracellular Traps Promote Aberrant Macrophages Activation in Behçet’s Disease

Frontiers in Immunology ◽

10.3389/fimmu.2020.590622 ◽

2021 ◽

Vol 11 ◽

Author(s):

Lu Li ◽

Xin Yu ◽

Jinjing Liu ◽

Zhimian Wang ◽

Chaoran Li ◽

...

Keyword(s):

Flow Cytometry ◽

T Cells ◽

Behcet’S Disease ◽

Behçet's Disease ◽

Histone H4 ◽

Behcet's Disease ◽

Extracellular Traps ◽

Tnf Α ◽

Ifn Γ

Neutrophil extracellular traps (NETs) are upregulated and promote thrombosis in Behçet’s disease (BD). However, whether NETs promote autoinflammation in BD remains unclear. This study aimed to investigate the potential role of NETs in promoting macrophage activation in BD. Firstly, we quantified NETs by measuring double-stranded DNA (dsDNA) using PicoGreen and calculating the proportion of NETosis. Then macrophages were stimulated with BD- or healthy controls (HC)-derived NETs, and IL-8 and TNF-α production and IFN-γ+ CD4+ T cells differentiation were measured using ELISA and flow cytometry, respectively. The protein components in NETs were analyzed by western blot. Macrophages were stimulated with Histone H4 neutralized NETs, and IL-8 and TNF-α production were measured using ELISA. The level of 8-hydroxydeoxyguanosine (8-OHdG) DNA in NETs was measured using ELISA. The levels of reactive oxygen species (ROS) in serum and neutrophils were measured using ROS probes by a microplate reader and flow cytometry. We found that circulating NETs and neutrophil-derived NETs were significantly higher in BD than HC. BD NETs stimulated macrophages produced higher levels of IL-8 and TNF-α, and promoted IFN-γ+ CD4+ T cells differentiation. BD NETs were enriched in Histone H4, and neutralizing Histone H4 abrogated the BD NETs-mediated IL-8 production by macrophages, but not TNF-α. Also, BD neutrophils produced more 8-OHdG DNA than HC neutrophils, and the percentage of 8-OHdG DNA in dsDNA from BD neutrophils was also higher than that of HC neutrophils. The ROS levels in serum and neutrophils were both higher in BD than HC. Our findings suggested that excessive BD NETs promoted macrophages activation and facilitated IFN-γ+ CD4+ T cells differentiation. Higher levels of Histone H4 and oxidized DNA in BD NETs might mediate macrophages hyperactivation.

Neutrophil Extracellular Traps in Host Defense

Cold Spring Harbor Perspectives in Biology ◽

10.1101/cshperspect.a037028 ◽

2019 ◽

Vol 12 (7) ◽

pp. a037028 ◽

Cited By ~ 6

Author(s):

Sabrina Sofia Burgener ◽

Kate Schroder

Keyword(s):

Host Defense ◽

Inhibition of Methylcholanthrene-induced Carcinogenesis by an Interferon γ Receptor–dependent Foreign Body Reaction

Journal of Experimental Medicine ◽

10.1084/jem.20011887 ◽

2002 ◽

Vol 195 (11) ◽

pp. 1479-1490 ◽

Cited By ~ 61

Author(s):

Zhihai Qin ◽

Hye-Jung Kim ◽

Jens Hemme ◽

Thomas Blankenstein

Keyword(s):

Dna Damage ◽

Foreign Body ◽

Host Defense ◽

Tissue Damage ◽

Defense Mechanisms ◽

Foreign Body Reaction ◽

Tumor Development ◽

Interferon Γ ◽

Ifn Γ ◽

Deficient Mice

The foreign body reaction is one of the oldest host defense mechanisms against tissue damage which involves inflammation, scarring, and encapsulation. The chemical carcinogen methylcholanthrene (MCA) induces fibrosarcoma and tissue damage in parallel at the injection site. Tumor development induced by MCA but not due to p53-deficiency is increased in interferon-γ receptor (IFN-γR)–deficient mice. In the absence of IFN-γR, MCA diffusion and DNA damage of surrounding cells is increased. Locally produced IFN-γ induces the formation of a fibrotic capsule. Encapsulated MCA can persist virtually life-long in mice without inducing tumors. Together, the foreign body reaction against MCA prevents malignant transformation, probably by reducing DNA damage. This mechanism is more efficient in the presence of IFN-γR. Our results indicates that inflammation and scarring, both suspected to contribute to malignancy, prevent cancer in certain situations.

Interferon-γ Regulates the Death of M. tuberculosis-Infected Macrophages

Journal of Cell Death ◽

10.4137/jcd.s2822 ◽

2010 ◽

Vol 3 ◽

pp. JCD.S2822 ◽

Cited By ~ 16

Author(s):

Jinhee Lee ◽

Hardy Kornfeld

Keyword(s):

Adaptive Immunity ◽

Host Defense ◽

Dna Cleavage ◽

Interferon Γ ◽

Macrophage Cell ◽

Independent Manner ◽

Ifn Γ ◽

Bacterial Replication ◽

Dying Cells ◽

Apoptosis And Necrosis

We previously described a caspase-independent death induced in macrophages by a high intracellular burden of Mycobacterium tuberculosis (Mtb). This death, with features of apoptosis and necrosis, releases viable bacilli for spreading infection. Interferon (IFN)-γ promotes survival of macrophages with a low intracellular Mtb load by inhibiting bacterial replication. Macrophages in naïve hosts are unable to restrict Mtb replication following aerosol transmission, but IFN-γ is increasingly present when adaptive immunity is expressed in the lungs ~2 weeks post-infection. We therefore investigated the effects of IFN-γ on macrophages challenged with Mtb at high multiplicity of infection (MOI). In contrast to the response at low MOI, IFN-γ accelerated the death of heavily infected macrophages and altered the characteristics of the dying cells. IFN-γ increased caspase-dependent DNA cleavage and apoptotic vesicle formation, but it also increased mitochondrial injury and release of LDH and HMGB1 in a caspase-independent manner. Adaptive immunity in tuberculosis (TB), mediated primarily by IFN-γ, has differential effects on Mtb-induced macrophage cell death depending on the intracellular bacillary load. While IFN-γ generally promotes host defense, our data suggest that its effects on heavily infected macrophages could also accelerate necrosis and spreading infection in TB disease.

The regulatory mechanism of neutrophil extracellular traps in cancer biological behavior

Cell & Bioscience ◽

10.1186/s13578-021-00708-z ◽

2021 ◽

Vol 11 (1) ◽

Author(s):

Hui Wang ◽

Yiyin Zhang ◽

Qianling Wang ◽

Xiaoli Wei ◽

Hua Wang ◽

...

Keyword(s):

Cell Death ◽

Host Defense ◽

Regulatory Mechanism ◽

Biological Behavior ◽

Molecular Pathways ◽

The Past ◽

Extracellular Traps ◽

Promote Tumor Growth ◽

Cancer Associated Thrombosis

AbstractAs the predominant host defense against pathogens, neutrophil extracellular traps (NETs) have attracted increasing attention due to their vital roles in infectious inflammation in the past few years. Interestingly, NETs also play important roles in noninfectious conditions, such as rheumatism and cancer. The process of NETs formation can be regulated and the form of cell death accompanied by the formation of NETs is regarded as “NETosis”. A large amount of evidence has confirmed that many stimuli can facilitate the release of NETs from neutrophils. Furthermore, it has been illustrated that NETs promote tumor growth and progression via many molecular pathways. Meanwhile, NETs also can promote metastasis in many kinds of cancers based on multiple studies. In addition, some researchs have found that NETs can promote coagulation and cancer-associated thrombosis. In the present review, it will highlight how NETosis, which is stimulated by various stimuli and signaling pathways, affects cancer biological behaviors via NETs. Given their crucial roles in cancer, NETs will become possible therapeutic targets for inhibiting proliferation, metastasis and thrombosis in cancer patients.