Neutrophil Extracellular Traps: The Biology of Chromatin Externalization

Sollberger, Gabriel; Tilley, Dorothea; Zychlinsky, Arturo

doi:10.1016/j.devcel.2018.01.019

Cited by 292 publications

(270 citation statements)

References 149 publications

Supporting

Mentioning

259

Contrasting

Unclassified

Order By: Relevance

“…Many studies have captured the role of intracellular ROS in the process of NET formation (39). Upon activation, the primary ROS produced by the neutrophils are superoxide anion and H 2 O 2 .…”

Section: Discussionmentioning

confidence: 99%

Oxidant sensor cation channel TRPM2 regulates neutrophil extracellular trap formation and protects against pneumoseptic bacterial infection

et al. 2018

View full text Add to dashboard Cite

Neutrophil extracellular trap (NET) formation constitutes an important extracellular antimicrobial function of neutrophils that plays a protective role in bacterial pneumonia. Formation of reactive oxygen species (ROS) such as highly diffusible hydrogen peroxide (HO) is a hallmark of oxidative stress during inflammatory lung conditions including pneumonia. However, the impact of exogenous ROS on NET formation and the signaling pathway involved in the process is not completely understood. Here we demonstrate that the ROS-sensing, nonselective, calcium-permeable channel transient receptor potential melastatin 2 (TRPM2) is required for NET formation in response to exogenous HO. This TRPM2-dependent HO-mediated NET formation involved components of autophagy and activation of AMPK and p38 MAPK, but not PI3K and AKT. Primary neutrophils from Trpm2 mice fail to activate this pathway with a block in NET release and a concomitant decrease in their antimicrobial capacity. Consequently, Trpm2 mice were highly susceptible to pneumonic infection with Klebsiella pneumoniae owing to an impaired NET formation and high bacterial burden despite increased neutrophil infiltration in their lungs. These results identify a key role of TRPM2 in regulating NET formation by exogenous ROS via AMPK/p38 activation and autophagy machinery, as well as a protective antimicrobial role of TRPM2 in pneumonic bacterial infection.-Tripathi, J. K., Sharma, A., Sukumaran, P., Sun, Y., Mishra, B. B., Singh, B. B., Sharma, J. Oxidant sensor cation channel TRPM2 regulates neutrophil extracellular trap formation and protects against pneumoseptic bacterial infection.

show abstract

Section: Discussionmentioning

confidence: 99%

Oxidant sensor cation channel TRPM2 regulates neutrophil extracellular trap formation and protects against pneumoseptic bacterial infection

et al. 2018

View full text Add to dashboard Cite

show abstract

“…The NETs contribute to pathogen elimination, and their microbicide activity has been studied mainly in the neutralization of bacteria, but their role in the response toward other types of pathogens is not yet clearly understood (54, 55). Sousa-Rocha et al demonstrated that trypomastigotes, and soluble T. cruzi antigens are capable of inducing NETs release on human neutrophils by activation of TLR2 and−4, and that this response depends on the activation of the respiratory burst and the production of reactive oxygen species.…”

Section: Innate Immunitymentioning

confidence: 99%

The Unsolved Jigsaw Puzzle of the Immune Response in Chagas Disease

2018

View full text Add to dashboard Cite

Trypanosoma cruzi interacts with the different arms of the innate and adaptive host's immune response in a very complex and flowery manner. The history of host-parasite co-evolution has provided this protozoan with means of resisting, escaping or subverting the mechanisms of immunity and establishing a chronic infection. Despite many decades of research on the subject, the infection remains incurable, and the factors that steer chronic Chagas disease from an asymptomatic state to clinical onset are still unclear. As the relationship between T. cruzi and the host immune system is intricate, so is the amount and diversity of scientific knowledge on the matter. Many of the mechanisms of immunity are fairly well understood, but unveiling the factors that lead each of these to success or failure, within the coordinated response as a whole, requires further research. The intention behind this Review is to compile the available information on the different aspects of the immune response, with an emphasis on those phenomena that have been studied and confirmed in the human host. For ease of comprehension, it has been subdivided in sections that cover the main humoral and cell-mediated components involved therein. However, we also intend to underline that these elements are not independent, but function intimately and concertedly. Here, we summarize years of investigation carried out to unravel the puzzling interplay between the host and the parasite.

show abstract

“…PMNs can also kill extracellular pathogens by degranulation, secretion of ROS, or the release of neutrophil extracellular traps (NETs). NETs consist of externalized decondensed chromatin decorated with granular proteins and histones to prevent the dissemination of pathogens . Serine proteases and histones provide antimicrobial activity against trapped pathogens.…”

Section: Intestinal and Invasive Nts Infectionsmentioning

confidence: 99%

Malaria, anemia, and invasive bacterial disease: A neutrophil problem?

Mooney

Galloway

Riley

2018

Journal of Leukocyte Biology

View full text Add to dashboard Cite

Invasive bacterial disease is well described in immunocompromised hosts, including those with malaria infection. One bacterial infection frequently observed in children with Plasmodium falciparum infection is nontyphoidal salmonella (NTS) infection, in which a typically intestinal infection becomes systemic with serious, often fatal, consequences. In this review, we consider the role of malaria‐induced immunoregulatory responses in tipping the balance from tissue homeostasis during malaria infection to risk of invasive NTS. Also, neutrophils are crucial in the clearance of NTS but their ability to mount an oxidative burst and kill intracellular Salmonella is severely compromised during, and for some time after, an acute malaria infection. Here, we summarize the evidence linking malaria and invasive NTS infections; describe the role of neutrophils in clearing NTS infections; review evidence for neutrophil dysfunction in malaria infections; and explore roles of heme oxygenase‐1, IL‐10, and complement in mediating this dysfunction. Finally, given the epidemiological evidence that low density, subclinical malaria infections pose a risk for invasive NTS infections, we consider whether the high prevalence of such infections might underlie the very high incidence of invasive bacterial disease across much of sub‐Saharan Africa.

show abstract

Neutrophil Extracellular Traps: The Biology of Chromatin Externalization

Cited by 292 publications

References 149 publications

Oxidant sensor cation channel TRPM2 regulates neutrophil extracellular trap formation and protects against pneumoseptic bacterial infection

Oxidant sensor cation channel TRPM2 regulates neutrophil extracellular trap formation and protects against pneumoseptic bacterial infection

The Unsolved Jigsaw Puzzle of the Immune Response in Chagas Disease

Malaria, anemia, and invasive bacterial disease: A neutrophil problem?

Contact Info

Product

Resources

About