Influence of CX3CR1 Deletion on Cochlear Hair Cell Survival and Macrophage Expression in Chronic Suppurative Otitis Media.
Journal
Otology & neurotology : official publication of the American Otological Society, American Neurotology Society [and] European Academy of Otology and Neurotology
ISSN: 1537-4505
Titre abrégé: Otol Neurotol
Pays: United States
ID NLM: 100961504
Informations de publication
Date de publication:
01 07 2023
01 07 2023
Historique:
pmc-release:
01
07
2024
medline:
16
6
2023
pubmed:
14
6
2023
entrez:
14
6
2023
Statut:
ppublish
Résumé
Our objective was to determine whether the receptor CX3CR1 is necessary for the recruitment of macrophages to the cochlea in chronic suppurative otitis media (CSOM) and if its deletion can prevent hair cell loss in CSOM. CSOM is a neglected disease that afflicts 330 million people worldwide and is the most common cause of permanent hearing loss among children in the developing world. It is characterized by a chronically discharging infected middle ear. We have previously demonstrated that CSOM causes macrophage associated sensory hearing loss. The receptor CX3CR1 is expressed on macrophages, which have been shown to be increased at the time point of outer hair cell (OHC) loss in CSOM. In this report, we examine the influence of CX3CR1 deletion (CX3CR1-/-) in a validated model of Pseudomonas aeruginosa (PA) CSOM. The data show no difference in OHC loss between the CX3CR1-/- CSOM group and CX3CR1+/+ CSOM group (p = 0.28). We observed partial OHC loss in the cochlear basal turn, no OHC loss in the middle and apical turns in both CX3CR1-/- and CX3CR1+/+ CSOM mice at 14 days after bacterial inoculation. No inner hair cell (IHC) loss was found in all cochlear turns in all groups. We also counted F4/80 labeled macrophages in the spiral ganglion, spiral ligament, stria vascularis and spiral limbus of the basal, middle, and apical turn in cryosections. We did not find a significant difference in the total number of cochlear macrophages between CX3CR1-/- mice and CX3CR1+/+ mice (p = 0.97). The data did not support a role for CX3CR1 macrophage associated HC loss in CSOM.
Sections du résumé
OBJECTIVE
Our objective was to determine whether the receptor CX3CR1 is necessary for the recruitment of macrophages to the cochlea in chronic suppurative otitis media (CSOM) and if its deletion can prevent hair cell loss in CSOM.
BACKGROUND
CSOM is a neglected disease that afflicts 330 million people worldwide and is the most common cause of permanent hearing loss among children in the developing world. It is characterized by a chronically discharging infected middle ear. We have previously demonstrated that CSOM causes macrophage associated sensory hearing loss. The receptor CX3CR1 is expressed on macrophages, which have been shown to be increased at the time point of outer hair cell (OHC) loss in CSOM.
METHODS
In this report, we examine the influence of CX3CR1 deletion (CX3CR1-/-) in a validated model of Pseudomonas aeruginosa (PA) CSOM.
RESULTS
The data show no difference in OHC loss between the CX3CR1-/- CSOM group and CX3CR1+/+ CSOM group (p = 0.28). We observed partial OHC loss in the cochlear basal turn, no OHC loss in the middle and apical turns in both CX3CR1-/- and CX3CR1+/+ CSOM mice at 14 days after bacterial inoculation. No inner hair cell (IHC) loss was found in all cochlear turns in all groups. We also counted F4/80 labeled macrophages in the spiral ganglion, spiral ligament, stria vascularis and spiral limbus of the basal, middle, and apical turn in cryosections. We did not find a significant difference in the total number of cochlear macrophages between CX3CR1-/- mice and CX3CR1+/+ mice (p = 0.97).
CONCLUSION
The data did not support a role for CX3CR1 macrophage associated HC loss in CSOM.
Identifiants
pubmed: 37315234
doi: 10.1097/MAO.0000000000003884
pii: 00129492-202307000-00023
pmc: PMC10275455
mid: NIHMS1884254
doi:
Substances chimiques
Cx3cr1 protein, mouse
0
CX3C Chemokine Receptor 1
0
Types de publication
Journal Article
Research Support, N.I.H., Extramural
Langues
eng
Sous-ensembles de citation
IM
Pagination
605-610Subventions
Organisme : NIDCD NIH HHS
ID : R01 DC019965
Pays : United States
Informations de copyright
Copyright © 2023, Otology & Neurotology, Inc.
Déclaration de conflit d'intérêts
The authors disclose no conflicts of interest.
Références
Monasta L, Ronfani L, Marchetti F, et al. Burden of disease caused by otitis media: systematic review and global estimates. PLoS One 2012;7:e36226.
Acuin J. Chronic suppurative otitis media : burden of illness and management options. World Health Organization . Switzerland: Word Health Organization; 2004.
Karela M, Berry S, Watkins A, Phillipps JJ. Myringoplasty: surgical outcomes and hearing improvement: is it worth performing to improve hearing? Eur Arch Otorhinolaryngol 2008;265:1039–42.
Aggarwal R, Saeed SR, Green KJ. Myringoplasty. J Laryngol Otol 2006;120:429–32.
Santa Maria PL, Kaufman AC, Bacacao B, et al. Topical therapy failure in chronic suppurative otitis media is due to persister cells in biofilms. Otol Neurotol 2021;42:e1263–72.
Dorr T, Vulic M, Lewis K. Ciprofloxacin causes persister formation by inducing the TisB toxin in Escherichia coli . PLoS Biol 2010;8:e1000317.
Donlan RM. Biofilms: microbial life on surfaces. Emerg Infect Dis 2002;8:881–90.
Dostert M, Belanger CR, Hancock REW. Design and assessment of anti-biofilm peptides: steps toward clinical application. J Innate Immun 2019;11:193–204.
Davies D. Understanding biofilm resistance to antibacterial agents. Nat Rev Drug Discov 2003;2:114–22.
Conlon BP, Rowe SE, Gandt AB, et al. Persister formation in Staphylococcus aureus is associated with ATP depletion. Nat Microbiol 2016;1:16051.
Khomtchouk KM, Kouhi A, Xia A, et al. A novel mouse model of chronic suppurative otitis media and its use in preclinical antibiotic evaluation. Sci Adv 2020;6:eabc1828.
Xia A, Thai A, Cao Z, et al. Chronic suppurative otitis media causes macrophage-associated sensorineural hearing loss. J Neuroinflammation 2022;19:224.
Jung S, Aliberti J, Graemmel P, et al. Analysis of fractalkine receptor CX(3)CR1 function by targeted deletion and green fluorescent protein reporter gene insertion. Mol Cell Biol 2000;20:4106–14.
Hirose K, Discolo CM, Keasler JR, Ransohoff R. Mononuclear phagocytes migrate into the murine cochlea after acoustic trauma. J Comp Neurol 2005;489:180–94.
Sato E, Shick HE, Ransohoff RM, Hirose K. Repopulation of cochlear macrophages in murine hematopoietic progenitor cell chimeras: the role of CX3CR1. J Comp Neurol 2008;506:930–42.
Claussen AD, Quevedo RV, Kirk JR, et al. Chronic cochlear implantation with and without electric stimulation in a mouse model induces robust cochlear influx of CX3CR1 +/GFP macrophages. Hear Res 2022;426:108510.
Sato E, Shick HE, Ransohoff RM, Hirose K. Expression of fractalkine receptor CX3CR1 on cochlear macrophages influences survival of hair cells following ototoxic injury. J Assoc Res Otolaryngol 2010;11:223–34.
Kaur T, Zamani D, Tong L, et al. Fractalkine signaling regulates macrophage recruitment into the cochlea and promotes the survival of spiral ganglion neurons after selective hair cell lesion. J Neurosci 2015;35:15050–61.
Kaur T, Clayman AC, Nash AJ, et al. Lack of fractalkine receptor on macrophages impairs spontaneous recovery of ribbon synapses after moderate noise trauma in C57BL/6 mice. Front Neurosci 2019;13:620.
Xia A, Song Y, Wang R, et al. Prestin regulation and function in residual outer hair cells after noise-induced hearing loss. PLoS One 2013;8:e82602.
Gunner G, Cheadle L, Johnson KM, et al. Sensory lesioning induces microglial synapse elimination via ADAM10 and fractalkine signaling. Nat Neurosci 2019;22:1075–88.
Dong Y, Zhang C, Frye M, et al. Differential fates of tissue macrophages in the cochlea during postnatal development. Hear Res 2018;365:110–26.
Lang H, Ebihara Y, Schmiedt RA, et al. Contribution of bone marrow hematopoietic stem cells to adult mouse inner ear: mesenchymal cells and fibrocytes. J Comp Neurol 2006;496:187–201.
Frye MD, Zhang C, Hu BH. Lower level noise exposure that produces only TTS modulates the immune homeostasis of cochlear macrophages. J Neuroimmunol 2018;323:152–66.
Yang W, Vethanayagam RR, Dong Y, Cai Q, Hu BH. Activation of the antigen presentation function of mononuclear phagocyte populations associated with the basilar membrane of the cochlea after acoustic overstimulation. Neuroscience 2015;303:1–15.
Frye MD, Yang W, Zhang C, Xiong B, Hu BH. Dynamic activation of basilar membrane macrophages in response to chronic sensory cell degeneration in aging mouse cochleae. Hear Res 2017;344:125–34.
Hirose K, Hartsock JJ, Johnson S, Santi P, Salt AN. Systemic lipopolysaccharide compromises the blood-labyrinth barrier and increases entry of serum fluorescein into the perilymph. J Assoc Res Otolaryngol 2014;15:707–19.
Liu W, Molnar M, Garnham C, Benav H, Rask-Andersen H. Macrophages in the human cochlea: saviors or predators-a study using super-resolution immunohistochemistry. Front Immunol 2018;9:223.
Rai V, Wood MB, Feng H, et al. The immune response after noise damage in the cochlea is characterized by a heterogeneous mix of adaptive and innate immune cells. Sci Rep 2020;10:15167.
Park JE, Barbul A. Understanding the role of immune regulation in wound healing. Am J Surg 2004;187:11S–6S.
Ladrech S, Wang J, Simonneau L, Puel JL, Lenoir M. Macrophage contribution to the response of the rat organ of corti to amikacin. J Neurosci Res 2007;85:1970–9.
Fujiwara N, Kobayashi K. Macrophages in inflammation. Curr Drug Targets Inflamm Allergy 2005;4:281–6.
Kaur T, Ohlemiller KK, Warchol ME. Genetic disruption of fractalkine signaling leads to enhanced loss of cochlear afferents following ototoxic or acoustic injury. J Comp Neurol 2018;526:824–35.