Attenuated TLRs in middle ear mucosa contributes to susceptibility of chronic suppurative otitis media

Yu, Shaohua; Zhang, Zhi Gang; Chen, Sui Jun; Zheng, Yi; Chen, Yu Bin; Liu, Yi; Jiang, Huaili; Feng, Lian; Huang, Xi

doi:10.1016/j.humimm.2014.05.009

Cited by 41 publications

(39 citation statements)

References 30 publications

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“…The predominant bacterial pathogens for CSOM -Pseudomonas aeruginosa and Staphylococcus aureus 83,84 -form biofilms with other otopathogens and elicit an increased innate inflammatory responses, which might contribute to the chronicity of OM and progression to CSOM despite appropriate intervention 84 . Evidence of the increased inflammation includes high levels of IL-8 in the middle ear fluid 85 and increased mRNA and protein levels of tumour necrosis factor (TNF), IL-1β, IL-6 and interferon-γ (IFNγ) in the middle ear mucosa compared with patients with chronic OME 86 .…”

Section: Middle Ear Effusion (Mee) 178mentioning

confidence: 99%

Otitis media

Schilder

Chonmaitree

Cripps

et al. 2016

Nat Rev Dis Primers

414

361

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Otitis media (OM) or middle ear inflammation is a spectrum of diseases, including acute otitis media (AOM), otitis media with effusion (OME; 'glue ear') and chronic suppurative otitis media (CSOM). OM is among the most common diseases in young children worldwide. Although OM may resolve spontaneously without complications, it can be associated with hearing loss and life-long sequelae. In developing countries, CSOM is a leading cause of hearing loss. OM can be of bacterial or viral origin; during 'colds', viruses can ascend through the Eustachian tube to the middle ear and pave the way for bacterial otopathogens that reside in the nasopharynx. Diagnosis depends on typical signs and symptoms, such as acute ear pain and bulging of the tympanic membrane (eardrum) for AOM and hearing loss for OME; diagnostic modalities include (pneumatic) otoscopy, tympanometry and audiometry. Symptomatic management of ear pain and fever is the mainstay of AOM treatment, reserving antibiotics for children with severe, persistent or recurrent infections. Management of OME largely consists of watchful waiting, with ventilation (tympanostomy) tubes primarily for children with chronic effusions and hearing loss, developmental delays or learning difficulties. The role of hearing aids to alleviate symptoms of hearing loss in the management of OME needs further study. Insertion of ventilation tubes and adenoidectomy are common operations for recurrent AOM to prevent recurrences, but their effectiveness is still debated. Despite reports of a decline in the incidence of OM over the past decade, attributed to the implementation of clinical guidelines that promote accurate diagnosis and judicious use of antibiotics and to pneumococcal conjugate vaccination, OM continues to be a leading cause for medical consultation, antibiotic prescription and surgery in high-income countries.

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Section: Middle Ear Effusion (Mee) 178mentioning

confidence: 99%

Otitis media

Schilder

Chonmaitree

Cripps

et al. 2016

Nat Rev Dis Primers

414

361

View full text Add to dashboard Cite

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“…IL-8 plays a role in the development of chronicity of OM and has also been related to bacterial growth. Increased mRNA as well as protein levels of TNF-a, IL-6, IL-1b and IFN-c have been found in the middle ear mucosa of CSOM patients compared with heathy individuals (Si et al, 2014). The upregulation of these pro-inflammatory cytokines can cause tissue damage as well as transition from acute to chronic OM.…”

Section: Pathogenesismentioning

confidence: 99%

Current concepts in the pathogenesis and treatment of chronic suppurative otitis media

Mittal

Lisi

Gerring

et al. 2015

Journal of Medical Microbiology

199

161

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Otitis media (OM) is an inflammation of the middle ear associated with infection. Despite appropriate therapy, acute OM (AOM) can progress to chronic suppurative OM (CSOM) associated with ear drum perforation and purulent discharge. The effusion prevents the middle ear ossicles from properly relaying sound vibrations from the ear drum to the oval window of the inner ear, causing conductive hearing loss. In addition, the inflammatory mediators generated during CSOM can penetrate into the inner ear through the round window. This can cause the loss of hair cells in the cochlea, leading to sensorineural hearing loss. Pseudomonas aeruginosa and Staphylococcus aureus are the most predominant pathogens that cause CSOM. Although the pathogenesis of AOM is well studied, very limited research is available in relation to CSOM. With the emergence of antibiotic resistance as well as the ototoxicity of antibiotics and the potential risks of surgery, there is an urgent need to develop effective therapeutic strategies against CSOM. This warrants understanding the role of host immunity in CSOM and how the bacteria evade these potent immune responses. Understanding the molecular mechanisms leading to CSOM will help in designing novel treatment modalities against the disease and hence preventing the hearing loss. IntroductionOtitis media (OM) refers to a group of complex infectious and inflammatory diseases affecting the middle ear (Dickson, 2014). OM in general is very common, as studies show that around 80 % of children should have experienced at least one episode by their third birthday (Teele et al., 1989). OM has been broadly classified into two main types, acute and chronic. Acute OM (AOM) is characterized by the rapid onset of signs of inflammation, specifically bulging and possible perforation of the tympanic membrane, fullness and erythema, as well as symptoms associated with inflammation such as otalgia, irritability and fever (Pukander, 1983;Harkness & Topham, 1998). Despite appropriate antibiotic therapy, AOM may progress to chronic suppurative OM (CSOM) characterized by persistent drainage from the middle ear associated with a perforated ear drum (Wintermeyer & Nahata, 1994;Harkness & Topham, 1998). When examined by otoscope, the middle ear looks red and inflamed with purulent discharge in CSOM patients (Figs 1 and 2). It is one of the most common chronic infectious diseases worldwide especially affecting children (Roland, 2002; Verhoeff et al., 2006). Hearing impairment is one of the most common sequelae of CSOM (Aarhus et al., 2015). The resultant hearing loss can have a negative impact on a child's speech development, education and behaviour (Olatoke et al., 2008; Khairi Md Daud et al., 2010). Mortality due to complications of CSOM is typically higher than other types of OM (Yorgancilar et al., 2013a;Qureishi et al., 2014). Intracranial complications like brain abscess and meningitis are the most common causes of death in CSOM patients (Dubey et al., 2010;Chew et al., 2012;Sun & Sun, 2014).In this article, the rec...

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“…58 A recent report has further confirmed these findings, demonstrating lower mRNA and protein levels of TLR2, TLR4, and TLR5 in middle ear mucosa of CSOM patients. 59 The down-regulation of TLR expression during OM can lead to inefficient host defense in the middle ear. This can cause repeated infections and persistent inflammations, eventually leading to recurrent, persistent suppurative chronic middle ear diseases.…”

Section: Epithelial Cellsmentioning

confidence: 99%

Role of innate immunity in the pathogenesis of otitis media

Mittal

Kodiyan

Gerring

et al. 2014

International Journal of Infectious Diseases

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Summary Otitis media (OM) is a public health problem in both developed and developing countries. It is the leading cause of hearing loss and represents a significant healthcare burden. In some cases, acute OM progresses to chronic suppurative OM (CSOM), characterized by effusion and discharge, despite antimicrobial therapy. The emergence of antibiotic resistance and potential ototoxicity of antibiotics has created an urgent need to design non-conventional therapeutic strategies against OM based on modern insights into its pathophysiology. In this article, we review the role of innate immunity as it pertains to OM and discuss recent advances in understanding the role of innate immune cells in protecting the middle ear. We also discuss the mechanisms utilized by pathogens to subvert innate immunity and thereby overcome defensive responses. A better knowledge about bacterial virulence and host resistance promises to reveal novel targets to design effective treatment strategies against OM. The identification and characterization of small natural compounds that can boost innate immunity may provide new avenues for the treatment of OM. There is also a need to design novel methods for targeted delivery of these compounds into the middle ear, allowing higher therapeutic doses and minimizing systemic side effects.

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Attenuated TLRs in middle ear mucosa contributes to susceptibility of chronic suppurative otitis media

Cited by 41 publications

References 30 publications

Otitis media

Otitis media

Current concepts in the pathogenesis and treatment of chronic suppurative otitis media

Role of innate immunity in the pathogenesis of otitis media

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