Role of Extracellular Trap Release During Bacterial and Viral Infection

Schultz, Bárbara M.; Acevedo, Orlando A.; Kalergis, Alexis M.; Bueno, Susan M.

doi:10.3389/fmicb.2022.798853

Cited by 42 publications

(25 citation statements)

References 200 publications

(301 reference statements)

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Since their discovery in 2004, ETs have been described from a wide variety of innate immune cells and are now widely regarded as an ancient and evolutionarily conserved host defense mechanism in the plant and animal kingdoms ( 119 , 120 ). Several pathogens can produce one or more nucleases to directly act on the DNA skeleton of ETs ( 6 ).…”

Section: Discussionmentioning

confidence: 99%

Pathogen-Derived Nucleases: An Effective Weapon for Escaping Extracellular Traps

et al. 2022

View full text Add to dashboard Cite

Since the 2004 publication of the first study describing extracellular traps (ETs) from human neutrophils, several reports have shown the presence of ETs in a variety of different animals and plants. ETs perform two important functions of immobilizing and killing invading microbes and are considered a novel part of the phagocytosis-independent, innate immune extracellular defense system. However, several pathogens can release nucleases that degrade the DNA backbone of ETs, reducing their effectiveness and resulting in increased pathogenicity. In this review, we examined the relevant literature and summarized the results on bacterial and fungal pathogens and parasites that produce nucleases to evade the ET-mediated host antimicrobial mechanism.

show abstract

Section: Discussionmentioning

confidence: 99%

Pathogen-Derived Nucleases: An Effective Weapon for Escaping Extracellular Traps

et al. 2022

View full text Add to dashboard Cite

show abstract

“…Neutrophils critically perform acute inflammatory duties including bacterial clearance and removal of dying cells, which is protective of tissues. Conversely, neutrophils can contribute to tissue damage in inflammatory diseases such as rheumatoid arthritis (RA) and systemic lupus erythematosus (SLE) [5; 40; 49]. In order to understand whether neutrophils/monocytes are protective or contribute to the progression of tissue damage in pulpitis, we performed a targeted depletion experiment of GR1+ cells.…”

Section: Discussionmentioning

confidence: 99%

Neuronal-immune Axis Alters Pain and Sensory Afferent Damage During Dental Pulp Injury

Erdoğan

Michot

Xia

et al. 2022

Preprint

View full text Add to dashboard Cite

Dental pulp tissue is densely innervated by afferent fibers of the trigeminal ganglion. When bacteria cause dental decay near the pulpal tissue, a strong neuronal and immune response occur, creating pulpitis, which is associated with severe pain and pulp tissue damage. Neuro-immune interactions have the potential to modulate both the pain and pathological outcome of pulpitis. We first investigated the role of the neuropeptide calcitonin-gene related peptide (CGRP), released from peptidergic sensory afferents, in dental pain and immune responses by using calca knock out (calca-/-) and wild type (calca+/+) mice, in a model of pulpitis by creating a mechanical exposure of the dental pulp horn. While CGRP did not contribute to facial mechanical hypersensitivity, at an early time point, it did contribute to spontaneous pain-like behavior. We also found that CGRP contributed to recruitment of neutrophils and monocytes, while not clearly affecting the progression of pulpal pathology histologically. When we depleted neutrophils and monocytes, we found that there was more sensory afferent loss, tissue damage and deeper spread of bacteria into the pulp tissue, while there was a reduction in facial mechanical hypersensitivity compared to control animals at a later time point. Overall, we showed that there is a crosstalk between peptidergic neurons and neutrophils in the pulp, modulating the pain and inflammatory outcomes of the disease.

show abstract

“…17 NETs are degraded by endogenous deoxyribonucleases (DNases), 18 as well as nucleases produced by pathogens to evade capture by NETs. 19 Although delayed NET digestion may contribute to thrombosis 18 and autoimmunity, 20 inappropriately rapid NET degradation liberates captured pathogens and releases toxic NET degradation products (NDPs) such as cell-free (cf) DNA, histones, MPO, and NE that induce tissue injury and inflammation. [21][22][23] Although intact NETs and digested NDPs are often described interchangeably, they are structurally and functionally distinct.…”

Section: Introductionmentioning

confidence: 99%

“…While much research focuses on the detrimental effects of excessive NETosis, NETs are conserved at various tiers of evolution, and when released in a well-regulated manner, they benefit the host by capturing and killing viral and bacterial pathogens, 6,19 serving as a sink to promote the clearance of inflammatory cytokines, 23 and helping to activate macrophages and T cells to combat infection and promote resolution of inappropriate inflammation. 32,33 Therefore, it is necessary to carefully tailor NET-directed treatment strategies to different disease states, perhaps employing therapeutics that block NETosis in autoimmune conditions driven by chronic sterile inflammation, while using treatments that neutralize NET toxicities but preserve their ability to capture pathogens in the setting of infection.…”

Section: Introductionmentioning

confidence: 99%

Building a better NET: Neutrophil extracellular trap targeted therapeutics in the treatment of infectious and inflammatory disorders

Ngo

Gollomp

2022

Research and Practice in Thrombosis and Haemostasis

View full text Add to dashboard Cite

Infectious and inflammatory stimuli induce the release of neutrophil extracellular traps (NETs), webs of cell‐free (cf) DNA complexed with histones and antimicrobial proteins, that capture and kill pathogens. Despite their protective role in the initial stages of sepsis, excessive NET release accompanied by NET degradation, leads to the release of NET degradation products (NDPs), including cfDNA, histones, and myeloperoxidase that injure the microvasculature. Murine studies have shown that clearance or neutralization of NDPs improves outcomes, demonstrating that NETs have a causal link to disease and are not merely biomarkers. Recently, elevated NDPs have been associated with disease severity in sepsis and coronavirus disease 2019, raising further interest in targeting NETs. Many propose eliminating NETs, either by preventing their release, or by degrading them. However, NET inhibition may impede the innate immune response and is difficult to achieve in rapid‐onset conditions such as sepsis. On the other hand, approaches that accelerate NET degradation have met with mixed results in murine studies, raising the concern that this strategy may liberate NET‐captured pathogens while increasing circulating levels of harmful NDPs. Alternative NET‐directed strategies include therapies that neutralize, sequester, or remove NDPs from the circulation. Others propose modifying released NETs to decrease their capacity to induce collateral tissue damage while enhancing their ability to capture microorganisms. Synthetic NETs have also been designed to combat antibiotic‐resistant organisms. Although it is still in its infancy, the field of NET‐targeted therapeutics is advancing rapidly and may soon find application in the treatment of sepsis and other inflammatory disorders.

show abstract

Role of Extracellular Trap Release During Bacterial and Viral Infection

Cited by 42 publications

References 200 publications

Pathogen-Derived Nucleases: An Effective Weapon for Escaping Extracellular Traps

Pathogen-Derived Nucleases: An Effective Weapon for Escaping Extracellular Traps

Neuronal-immune Axis Alters Pain and Sensory Afferent Damage During Dental Pulp Injury

Building a better NET: Neutrophil extracellular trap targeted therapeutics in the treatment of infectious and inflammatory disorders

Contact Info

Product

Resources

About