Eosinophils releasing DNA traps

Eosinophils: More Than Just Cell Death?

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Elliot Brynn in Health & Wellness December 2025 • 4 min read.

"Unpacking the Debate Around Eosinophil Cytolysis and Extracellular Trap Formation"


Eosinophils, a type of white blood cell, are key players in inflammatory conditions like asthma and nasal polyps. Recent research has focused on how these cells contribute to tissue inflammation, particularly through the formation of eosinophil extracellular traps (EETs).

A central question in this research area is whether eosinophil cell death (cytolysis) is necessary for EET formation. Persson and Ueki commented on a recent article, sparking a debate about this very topic. This article will further explore the nuances of eosinophil behavior, EET formation, and the role of cell death in these processes.

We aim to clarify the current understanding of eosinophil function, addressing whether cell death is a prerequisite for EET formation or if these are independent events. By unpacking this debate, we can better understand the complexities of eosinophil activity and its impact on inflammatory diseases.

Eosinophil Cytolysis and EET Formation: Are They Linked?

Eosinophils releasing DNA traps

The idea that inhibiting eosinophil apoptosis contributes to tissue eosinophilia is well-established. However, the relationship between eosinophil apoptosis, cytolysis, and EET formation is more complex.

It's crucial to recognize that inhibiting eosinophil apoptosis and inducing cytolysis are not mutually exclusive events. For example, interleukin-5 (IL-5) can inhibit apoptosis and trigger cytolysis. This dual functionality highlights the intricate nature of eosinophil regulation.

  • RIPK3-MLKL Pathway: Eosinophil cytolysis depends on the receptor-interacting protein kinase 3 (RIPK3)-mixed lineage kinase-like (MLKL) pathway.
  • EET Formation: The formation of extracellular DNA traps can occur independently of the RIPK3-MLKL pathway.
  • Independent Processes: This suggests that EET formation and eosinophil cytolysis are distinct phenomena.
This distinction is important because it challenges the assumption that cell death is a prerequisite for EET formation. While viable eosinophils can undergo cytolysis, EETs can be generated from viable, non-lyzed cells. This suggests a sequential process where eosinophils first form EETs and then undergo cytolysis.

Rethinking EETosis: The Future of Eosinophil Research

Given the complexities, the term "EETosis," implying that eosinophil death is required for EET formation, may be a misnomer. Lyzed granulocytes produce a DNA cloud, whereas EETs are defined by DNA fibers.

The coexistence of EETs and clusters of extracellular granules in tissues can be explained by sequential participation of the same eosinophil in EET formation and subsequent cytolysis. Therefore, understanding the distinct mechanisms and triggers for EET formation and eosinophil cytolysis is essential for developing targeted therapies.

Further research should focus on the specific signals that initiate each process and how these pathways can be modulated to reduce inflammation without compromising host defense mechanisms. A more nuanced understanding of eosinophil behavior will pave the way for more effective treatments for eosinophil-associated inflammatory diseases.

About this Article -

This article was crafted using a human-AI hybrid and collaborative approach. AI assisted our team with initial drafting, research insights, identifying key questions, and image generation. Our human editors guided topic selection, defined the angle, structured the content, ensured factual accuracy and relevance, refined the tone, and conducted thorough editing to deliver helpful, high-quality information.See our About page for more information.

Everything You Need To Know

1

What are Eosinophils, and why are they important?

Eosinophils are a type of white blood cell that play a significant role in inflammatory conditions such as asthma and nasal polyps. Their importance lies in their contribution to tissue inflammation. The implications of their activity directly impact the severity and progression of these diseases.

2

What are Eosinophil extracellular traps (EETs) and what is their significance?

Eosinophil extracellular traps (EETs) are structures made by Eosinophils. These are extracellular DNA traps formed by the Eosinophils. Their significance is highlighted by the ongoing research into their formation and the debate surrounding the role of cell death in their creation. Understanding EETs is crucial for treating inflammatory conditions. The implications are significant in understanding how Eosinophils contribute to inflammation, and how to potentially stop it.

3

What is the RIPK3-MLKL pathway, and what is its role?

The receptor-interacting protein kinase 3 (RIPK3)-mixed lineage kinase-like (MLKL) pathway is involved in Eosinophil cytolysis. The significance lies in the fact that Eosinophil cytolysis depends on this pathway. The implications of this pathway being involved are that it provides a potential target for therapeutic interventions aimed at modulating Eosinophil behavior and its effects on inflammation.

4

Are inhibiting Eosinophil apoptosis and inducing cytolysis the same thing?

Inhibiting Eosinophil apoptosis and inducing cytolysis are not mutually exclusive. The implications are that the regulation of Eosinophil behavior is complex, and interventions targeting these processes may have multifaceted effects. This understanding is important when developing targeted therapies.

5

Why might the term "EETosis" be a misnomer?

EETosis is a term that may be misleading as it implies Eosinophil death is required for EET formation, which is not always the case. It is significant because it challenges the assumption that cell death is a prerequisite for EET formation, as EETs can be generated from viable cells. This changes our understanding of the sequence of events. The implications mean that research needs to focus on the specific processes involved in both EET formation and Eosinophil cytolysis, and reconsider the terminology used to describe these events.

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