Eosinophilic Otitis Media: the Aftermath of Eosinophil Extracellular Trap Cell Death

Abstract

Unlike chronic otitis media, EOM is strongly associated with an allergic background. Corticosteroids are currently the only effective pharmacological treatment, and surgical intervention is often required. Mucosal eosinophils infiltrate extensively into the middle ear cavity where they are stimulated by locally produced activators including interleukin-5 and eotaxin. The eosinophils undergo cytolysis in the effusion, which represents a major fate of activated eosinophils in vivo. Recent data revealed cytolysis could be renamed as extracellular trap cell death (ETosis). ETosis represents suicidal cell death involving total cell degranulation and development of sticky chromatin structures (extracellular traps (ETs)). The characteristics of eosinophil- and neutrophil-derived ET polymers might contribute to the difference in viscosity of secretions between EOM and common chronic otitis media. The extracellular products remaining after eosinophil ETosis are an important aspect of EOM pathology. The concept of ETosis also has novel implications for potential therapeutic modalities in various eosinophilic disorders.

Eosinophilic otitis media and eosinophilic asthma: Shared pathophysiology and response to anti-IL5

“…including highly cationic proteins which are directly toxic to pathogens but also to the tissue. High levels of eosinophil granule proteins in the middle ear effusion appear to cause epithelial damage and decrease mucus transport in the Eustachian tube [9]. Patient with EOM suffer from recurrent highly viscous middle ear effusions and are at high risk of progressive perceptive hearing loss.…”

Sialodochitis fibrinosa: Salivary duct obstruction by eosinophil extracellular traps?

“…A novel, rapid cell death pathway that involves release of web‐like chromatin structures (eosinophil extracellular traps [EETs]) has been recognised as eosinophil extracellular trap cell death (EETosis) (Ueki et al., 2013). In contrast to apoptosis, EETotic cells do not display “find me” signals before plasma membrane disruption, preventing pre‐emptive clearance by phagocytes (Ueki, Ohta, Takeda, Konno, & Hirokawa, 2017). Thus far, EETosis has been shown to represent cytolytic degranulation that occurs in diverse eosinophil‐associated diseases (Mukherjee, Lacy, & Ueki, 2018).…”

Subversion of host immune responses by otopathogens during otitis media

“…In addition to NETs, eosinophilic extracellular traps (ETs) have been implicated in the pathogenesis of OM. ETs are associated with eosinophilic OM (EOM) and appear to facilitate the release of eosinophilic granules as well as DNA traps to destroy pathogens . Eosinophils and mast cells, which both contribute to T h 2 host cell immunity, are often found in COM infections .…”

“…Eosinophils in the middle ear are activated by cytokines such as IL‐5 and eotaxin. Eventually, eosinophils undergo extracellular trap cell death, also known as ETosis . ETosis involves cell death that results in the creation of extracellular traps (ETs), which play an important role in eosinophilic OM .…”

“…Eventually, eosinophils undergo extracellular trap cell death, also known as ETosis . ETosis involves cell death that results in the creation of extracellular traps (ETs), which play an important role in eosinophilic OM . The mechanism by which these eosinophilic traps promote evasion of immunity by otopathogens is through an increased amount of eosinophilic secretions, resulting in increased viscosity .…”