Basic Science Concepts in Otitis Media Pathophysiology and Immunity: Role of Mucins and Inflammation

Val, Stéphanie

doi:10.1007/978-3-319-17888-2_7

Cited by 7 publications

(12 citation statements)

References 149 publications

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“…Filamentous protein-like structures were also noted associated with the vesicles, similar to what was reported by Kesimer et al in exosomes isolated from airway epithelium (35). The global analysis of MEE exosomal miRNAs and proteins using IPA confirmed the importance of middle ear inflammation during COM, and the implication of IL-8 related responses (13,40). This finding is in line with our recent report of NETs predominance in COM effusions.…”

Section: Discussionsupporting

confidence: 91%

“…The progression of OM from acute OM (AOM) to COM, has long been shown to be in part under the influence of proinflammatory mediators, specifically through bacterial activation of epithelial proinflammatory pathways (reviewed in (13)), that drive middle ear epithelial remodeling into a pseudostratified epithelium in COM able to potently produce mucins (14)(15)(16). Recently, exosomes have been described as important mediators of intercellular communication.…”

mentioning

confidence: 99%

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Purification and characterization of microRNAs within middle ear fluid exosomes: implication in otitis media pathophysiology

et al. 2017

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Section: Discussionsupporting

confidence: 91%

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confidence: 99%

Purification and characterization of microRNAs within middle ear fluid exosomes: implication in otitis media pathophysiology

et al. 2017

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“…COME middle ear effusions ( 6 ) are most frequently mucoid ( 7 – 9 ) and viscous. It has been shown to be primarily composed of innate immunity mediators and among them from neutrophils ( 10 , 11 ), such as neutrophil extracellular traps (NETs) ( 12 , 13 ) along with secretory mucin glycoproteins, predominantly MUC5B ( 14 ) and a high level of pro-inflammatory cytokines especially interleukin 8 IL-8 (see review ( 15 )). Less frequently, COME MEEs are not as viscous and are characterized as serous.…”

Section: Introductionmentioning

confidence: 99%

Characterization of mucoid and serous middle ear effusions from patients with chronic otitis media: implication of different biological mechanisms?

et al. 2018

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BackgroundChronic Otitis Media with effusion (COME) is characterized by persistent middle ear effusions that are in most cases highly viscous, but some patients present with serous fluid. This study aimed at comprehensively characterizing the macromolecular composition of mucoid vs. serous MEEs.MethodsMEEs from patients with COME were analyzed for proteins by Mass Spectrometry (MS) and western blot techniques, total DNA quantity, bacterial DNA (16S sequencing) and cytokine content. Proteomics datasets were studied in Ingenuity pathway analysis (IPA).ResultsMucoid samples showed a global tendency of increased pro- inflammatory mediators. IL1-β and IL-10 were significantly more abundant in serous samples (p<0.01). Mucoid samples had higher DNA quantity (p=0.04), more likely to be positive in MUC5B protein (p=0.008) and higher peptide counts (12786 vs 2225), as well as an overall larger number of identified proteins (331 vs 177), compared to serous. IPA found the mucoid sample dataset to be related to immune cell function and epithelial remodeling whereas the serous sample dataset showed acute responses and blood related proteins. Interestingly, serous samples showed more bacterial DNA than mucoid ones, with less bacterial genera variability.ConclusionThis study demonstrates divergent immune responses in children with COME by effusion quality.

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“…It has been well-demonstrated that during this process, the healthy single layered middle ear epithelium remodels into a pseudo stratified epithelium in COM able to potently produce mucins[ 15 , 16 , 17 ]. This process has long been thought to be influenced by pro-inflammatory mediators, specifically through bacterial activation of epithelial proinflammatory pathways (reviewed in [ 18 ]). Some have attributed the progression from AOM to COM as an ‘allergic’ response characterized by presence of eosin eosinophilic markers and mediators in middle ear effusion (MEE)[ 19 ].…”

Section: Introductionmentioning

confidence: 99%

Proteomic Characterization of Middle Ear Fluid Confirms Neutrophil Extracellular Traps as a Predominant Innate Immune Response in Chronic Otitis Media

et al. 2016

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BackgroundChronic Otitis Media (COM) is characterized by middle ear effusion (MEE) and conductive hearing loss. MEE reflect mucus hypersecretion, but global proteomic profiling of the mucosal components are limited.ObjectiveThis study aimed at characterizing the proteome of MEEs from children with COM with the goal of elucidating important innate immune responses.MethodMEEs were collected from children (n = 49) with COM undergoing myringotomy. Mass spectrometry was employed for proteomic profiling in nine samples. Independent samples were further analyzed by cytokine multiplex assay, immunoblotting, neutrophil elastase activity, next generation DNA sequencing, and/or immunofluorescence analysis.Results109 unique and common proteins were identified by MS. A majority were innate immune molecules, along with typically intracellular proteins such as histones and actin. 19.5% percent of all mapped peptide counts were from proteins known to be released by neutrophils. Immunofluorescence and immunoblotting demonstrated the presence of neutrophil extracellular traps (NETs) in every MEE, along with MUC5B colocalization. DNA found in effusions revealed unfragmented DNA of human origin.ConclusionProteomic analysis of MEEs revealed a predominantly neutrophilic innate mucosal response in which MUC5B is associated with NET DNA. NETs are a primary macromolecular constituent of human COM middle ear effusions.

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Basic Science Concepts in Otitis Media Pathophysiology and Immunity: Role of Mucins and Inflammation

Cited by 7 publications

References 149 publications

Purification and characterization of microRNAs within middle ear fluid exosomes: implication in otitis media pathophysiology

Purification and characterization of microRNAs within middle ear fluid exosomes: implication in otitis media pathophysiology

Characterization of mucoid and serous middle ear effusions from patients with chronic otitis media: implication of different biological mechanisms?

Proteomic Characterization of Middle Ear Fluid Confirms Neutrophil Extracellular Traps as a Predominant Innate Immune Response in Chronic Otitis Media

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