Eosinophil extracellular vesicles and DNA traps in allergic inflammation

Abstract

Eosinophil granulocytes, a specialized subset of white blood cells, have traditionally been associated with allergic responses and parasitic infections. However, recent research has unveiled their versatile roles in immune regulation beyond these classical functions. This review highlights the emerging field of eosinophil biology, with a particular focus on their release of extracellular vesicles (EVs) and extracellular DNA traps (EETs). It further explores potential implications of eosinophil-derived EVs and EETs for immune responses during inflammatory diseases. The release of EVs/EETs from eosinophils, which also affects the eosinophils themselves, may influence both local and systemic immune reactions, affecting the pathophysiology of conditions such as airway inflammation, chronic rhinosinusitis and atopic dermatitis.

Keywords: EETosis; eosinophil activation; eosinophilic diseases; extracellular vesicles; inflammation; sombrero vesicles.

Figure 1

Extracellular eosinophil sombrero vesicles (eoSVs) are hallmarks of eosinophilic inflammation. (A) C-shaped and typical EoSVs are shown in three dimensions (3D) by electron tomography. (B) Representative electron micrograph of hypereosinophilic syndrome (HES) skin shows free EoSVs (colored in pink) in proximity to free extracellular granules (FEGs). (C) High magnification of extracellular tissue EoSVs with intact membranes and elongated, C-shaped, and typical morphologies. Reprinted from Neves et al., 2024 (26) under a Creative Commons Attribution 4.0 International (CC BY 4.0).

Figure 2

Human eosinophils undergo EETosis in response to stimulation with agonists. (A,B) Immunofluorescence for isotype (A) or anti-citrullinated H3 histone (CitH3) antibodies. Eosinophil extracellular traps (EETs) appear as filamentous chromatin structures immunolabeled for CitH3 (green) and DNA (Hoechst, blue). (Bi) Merged images of CitH3 +DNA-stained eosinophils in higher magnification. Arrows indicate EETs. Differential interference contrast (DIC) images were obtained by confocal microscopy. Purified eosinophils were stimulated with platelet activating factor (PAF) + IL-5. Ab, antibody. Images were reprinted from Neves et al., 2022 (13) under a Creative Commons Attribution 4.0 International (CC BY 4.0) license.