Chronic suppurative otitis media causes macrophage-associated sensorineural hearing loss.

Animals Child Chronic Disease Hearing Loss, Sensorineural / etiology Humans Macrophages Mice Otitis Media, Suppurative / complications
CSOM Cytokines HC loss Macrophages PA SNHL

Journal

Journal of neuroinflammation
ISSN: 1742-2094
Titre abrégé: J Neuroinflammation
Pays: England
ID NLM: 101222974

Informations de publication

Date de publication:
12 Sep 2022
Historique:
received: 23 03 2022
accepted: 23 08 2022
entrez: 12 9 2022
pubmed: 13 9 2022
medline: 15 9 2022
Statut: epublish

Résumé

Chronic suppurative otitis media (CSOM) is the most common cause of permanent hearing loss in children in the developing world. A large component of the permanent hearing loss is sensory in nature and our understanding of the mechanism of this has so far been limited to post-mortem human specimens or acute infection models that are not representative of human CSOM. In this report, we assess cochlear injury in a validated Pseudomonas aeruginosa (PA) CSOM mouse model. We generated persisters (PCs) and inoculated them into the mouse middle ear cavity. We tracked infection with IVIS and detected PA using RT-PCR. We assessed cochlear damage and innate immunity by Immunohistochemistry. Finally, we evaluated cytokines with multiplex assay and quantitative real-time PCR. We observed outer hair cell (OHC) loss predominantly in the basal turn of the cochlear at 14 days after bacterial inoculation. Macrophages, not neutrophils are the major immune cells in the cochlea in CSOM displaying increased numbers and a distribution correlated with the observed cochlear injury. The progression of the morphological changes suggests a transition from monocytes into tissue macrophages following infection. We also show that PA do not enter the cochlea and live bacteria are required for cochlear injury. We characterized cytokine activity in the CSOM cochlea. Taken together, this data shows a critical role for macrophages in CSOM-mediated sensorineural hearing loss (SNHL).

Sections du résumé

BACKGROUND BACKGROUND
Chronic suppurative otitis media (CSOM) is the most common cause of permanent hearing loss in children in the developing world. A large component of the permanent hearing loss is sensory in nature and our understanding of the mechanism of this has so far been limited to post-mortem human specimens or acute infection models that are not representative of human CSOM. In this report, we assess cochlear injury in a validated Pseudomonas aeruginosa (PA) CSOM mouse model.
METHODS METHODS
We generated persisters (PCs) and inoculated them into the mouse middle ear cavity. We tracked infection with IVIS and detected PA using RT-PCR. We assessed cochlear damage and innate immunity by Immunohistochemistry. Finally, we evaluated cytokines with multiplex assay and quantitative real-time PCR.
RESULTS RESULTS
We observed outer hair cell (OHC) loss predominantly in the basal turn of the cochlear at 14 days after bacterial inoculation. Macrophages, not neutrophils are the major immune cells in the cochlea in CSOM displaying increased numbers and a distribution correlated with the observed cochlear injury. The progression of the morphological changes suggests a transition from monocytes into tissue macrophages following infection. We also show that PA do not enter the cochlea and live bacteria are required for cochlear injury. We characterized cytokine activity in the CSOM cochlea.
CONCLUSIONS CONCLUSIONS
Taken together, this data shows a critical role for macrophages in CSOM-mediated sensorineural hearing loss (SNHL).

Identifiants

DOI: 10.1186/s12974-022-02585-w PMID: 36096817 PMC: PMC9465898
pubmed: 36096817
doi: 10.1186/s12974-022-02585-w
pii: 10.1186/s12974-022-02585-w
pmc: PMC9465898
doi:

Types de publication

Journal Article

Langues

eng

Sous-ensembles de citation

IM

Pagination

224

Informations de copyright

© 2022. The Author(s).

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Auteurs

Anping Xia (A)

Department of Otolaryngology-Head and Neck Surgery, School of Medicine, Stanford University, Palo Alto, CA, 94305, USA. apxia@stanford.edu.

Anthony Thai (A)

Department of Otolaryngology-Head and Neck Surgery, School of Medicine, Stanford University, Palo Alto, CA, 94305, USA.

Zhixin Cao (Z)

Department of Pathology, Shandong Provincial Hospital Affiliated to Shandong First Medical University, Jinan, Shandong Province, China.

Xiaohua Chen (X)

Department of Otolaryngology-Head and Neck Surgery, the First Affiliated Hospital, Zhengzhou University, Zhengzhou, Henan Province, China.

Jing Chen (J)

Department of Otolaryngology-Head and Neck Surgery, School of Medicine, Stanford University, Palo Alto, CA, 94305, USA.

Brian Bacacao (B)

Department of Otolaryngology-Head and Neck Surgery, School of Medicine, Stanford University, Palo Alto, CA, 94305, USA.

Laurent A Bekale (LA)

Department of Otolaryngology-Head and Neck Surgery, School of Medicine, Stanford University, Palo Alto, CA, 94305, USA.

Viktoria Schiel (V)

Department of Otolaryngology-Head and Neck Surgery, School of Medicine, Stanford University, Palo Alto, CA, 94305, USA.

Paul L Bollyky (PL)

Department of Medicine, Infectious Diseases, Stanford University, Stanford, Palo Alto, CA, 94305, USA.

Peter L Santa Maria (PLS)

Department of Otolaryngology-Head and Neck Surgery, School of Medicine, Stanford University, Palo Alto, CA, 94305, USA. petersantamaria@stanford.edu.

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Classifications MeSH

questionsmedicales.fr › Eucaryotes › Animaux › Chronic suppurative otitis media causes...
questionsmedicales.fr › Personnes › Tranches d'âge › Enfant › Chronic suppurative otitis media causes...
questionsmedicales.fr › États, signes et symptômes pathologiques › Processus pathologiques › Caractéristiques de la maladie › Maladie chronique › Chronic suppurative otitis media causes...
questionsmedicales.fr › États, signes et symptômes pathologiques › Signes et symptômes › Manifestations neurologiques › Troubles sensitifs › Troubles de l'audition › Perte d'audition › Surdité neurosensorielle › Chronic suppurative otitis media causes...
questionsmedicales.fr › Eucaryotes › Animaux › Chordés › Vertébrés › Mammifères › Eutheria › Primates › Haplorhini › Catarrhini › Hominidae › Humains › Chronic suppurative otitis media causes...
questionsmedicales.fr › Systèmes sanguin et immunitaire › Système immunitaire › Phagocytes › Macrophages › Chronic suppurative otitis media causes...
questionsmedicales.fr › Eucaryotes › Animaux › Chordés › Vertébrés › Mammifères › Eutheria › Rodentia › Muridae › Murinae › Souris › Chronic suppurative otitis media causes...
questionsmedicales.fr › Maladies oto-rhino-laryngologiques › Maladies des oreilles › Otite › Otite moyenne › Otite moyenne suppurée › Chronic suppurative otitis media causes...