High concentrations of middle ear antimicrobial peptides and proteins and proinflammatory cytokines are associated with detection of middle ear pathogens in children with recurrent acute otitis media

Seppanen, Elke; Thornton, Ruth B.; Corscadden, Karli J.; Granland, Caitlyn; Hibbert, Julie; Fuery, Angela; Wiertsema, Selma P.; Vijayasekaran, Shyan; Coates, Harvey; Jacoby, Peter; Currie, Andrew; Richmond, Peter; Kirkham, Lea‐Ann S.

doi:10.1371/journal.pone.0227080

Cited by 10 publications

(13 citation statements)

References 52 publications

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“…Signalling regulation by host and pathogen factors within the middle ear during OM may lead to modification of timing and secretion of various cytokines, chemokines, interferons, and antimicrobial peptides from the mucosal epithelium or cells recruited to the site of activation. Importantly, the concentrations of antimicrobial peptides and proteins, and cytokines within MEF of children experiencing recurrent AOM are known to increase (Seppanen et al, 2019).…”

Section: Pathogen Recognition and Activation Of Signalling Pathways Within The Innate Immune Responsementioning

confidence: 99%

“…Furthermore, in humans, lysozyme and ßdefensin 2 can synergistically partner to directly kill invading S. pneumoniae 6B (Lee et al, 2004) and protect against NTHi induced OM (Woo J. I. et al, 2014). Most recently, a study examining middle ear effusate from children experiencing recurrent AOM confirmed the importance of elevated antimicrobial protein (AP) and cytokines as potential markers for bacterial persistence and inflammation (Seppanen et al, 2019). Antimicrobial proteins or host defence peptides may offer future treatment options against polymicrobial infections (Bergenfelz and Hakansson, 2017;Batoni et al, 2021).…”

Section: Antimicrobial Factors Released By the Mucosal Epitheliummentioning

confidence: 99%

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Innate Immunity in the Middle Ear Mucosa

Massa

Spann

Cripps

2021

Front. Cell. Infect. Microbiol.

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Otitis media (OM) encompasses a spectrum of clinical presentations ranging from the readily identifiable Acute OM (AOM), which is characterised by otalgia and fever, to chronic otitis media with effusion (COME) where impaired hearing due to middle ear effusion may be the only clinical symptom. Chronic suppurative OM (CSOM) presents as a more severe form of OM, involving perforation of the tympanic membrane. The pathogenesis of OM in these varied clinical presentations is unclear but activation of the innate inflammatory responses to viral and/or bacterial infection of the upper respiratory tract performs an integral role. This localised inflammatory response can persist even after pathogens are cleared from the middle ear, eustachian tubes and, in the case of respiratory viruses, even the nasal compartment. Children prone to OM may experience an over exuberant inflammatory response that underlies the development of chronic forms of OM and their sequelae, including hearing impairment. Treatments for chronic effusive forms of OM are limited, with current therapeutic guidelines recommending a “watch and wait” strategy rather than active treatment with antibiotics, corticosteroids or other anti-inflammatory drugs. Overall, there is a clear need for more targeted and effective treatments that either prevent or reduce the hyper-inflammatory response associated with chronic forms of OM. Improved treatment options rely upon an in-depth understanding of OM pathogenesis, particularly the role of the host innate immune response during acute OM. In this paper, we review the current literature regarding the innate immune response within the middle ear to bacterial and viral otopathogens alone, and as co-infections. This is an important consideration, as the role of respiratory viruses as primary pathogens in OM is not yet fully understood. Furthermore, increased reporting from PCR-based diagnostics, indicates that viral/bacterial co-infections in the middle ear are more common than bacterial infections alone. Increasingly, the mechanisms by which viral/bacterial co-infections may drive or maintain complex innate immune responses and inflammation during OM as a chronic response require investigation. Improved understanding of the pathogenesis of chronic OM, including host innate immune response within the middle ear is vital for development of improved diagnostic and treatment options for our children.

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Section: Pathogen Recognition and Activation Of Signalling Pathways Within The Innate Immune Responsementioning

confidence: 99%

Section: Antimicrobial Factors Released By the Mucosal Epitheliummentioning

confidence: 99%

Innate Immunity in the Middle Ear Mucosa

Massa

Spann

Cripps

2021

Front. Cell. Infect. Microbiol.

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“…In these contexts, antimicrobial peptides (AMPs) are used as promising alternatives to counter bacterial infections and control microbial spreading. As antimicrobial resistance (AMR) is currently becoming a worldwide threat, the main focuses of research are: (i) to identify existing or new AMPs and to characterize their efficacy against prevalent microorganisms, including their mechanism of action and toxicity toward mammalian cells and/or blood cells; (ii) to assess the role of AMPs in modulating the pro-inflammatory cytokines and in adaptive immune mechanisms; and (iii) to identify new approaches for AMPs delivery [9].…”

Section: Introductionmentioning

confidence: 99%

An Update on Antimicrobial Peptides (AMPs) and Their Delivery Strategies for Wound Infections

2020

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Bacterial infections occur when wound healing fails to reach the final stage of healing, which is usually hindered by the presence of different pathogens. Different topical antimicrobial agents are used to inhibit bacterial growth due to antibiotic failure in reaching the infected site, which is accompanied very often by increased drug resistance and other side effects. In this review, we focus on antimicrobial peptides (AMPs), especially those with a high potential of efficacy against multidrug-resistant and biofilm-forming bacteria and fungi present in wound infections. Currently, different AMPs undergo preclinical and clinical phase to combat infection-related diseases. AMP dendrimers (AMPDs) have been mentioned as potent microbial agents. Various AMP delivery strategies that are used to combat infection and modulate the healing rate—such as polymers, scaffolds, films and wound dressings, and organic and inorganic nanoparticles—have been discussed as well. New technologies such as Clustered Regularly Interspaced Short Palindromic Repeat (CRISPR)-associated protein (CRISPR-Cas) are taken into consideration as potential future tools for AMP delivery in skin therapy.

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“…The middle ear is encased in a bony cavity, despite rich vascular supply, it is hard to maintain sufficient concentration of antibiotics when given orally ( Barry et al, 1997 ). The concentration of β-lactam antibiotics transferred to the middle ear cavity is at about only 10–15% of the blood concentration ( Figueira et al, 2016 ; Seppanen et al, 2019 ). In addition, the tympanic membrane of AOM patients becomes thicker, which is a barrier for topical antimicrobial treatment.…”

Section: Introductionmentioning

confidence: 99%

Novel Antimicrobial Treatment Strategy Based on Drug Delivery Systems for Acute Otitis Media

et al. 2021

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Despite tremendous success of pneumococcal conjugated vaccine and antimicrobial treatment by amoxicillin, acute otitis media (AOM) still remains as a great medical concern. Failure of antimicrobial treatment includes several factors. The middle ear cavity is surrounded by bone tissue, which makes it difficult to maintain sufficient concentration of antibiotics. Tympanic membrane of AOM patients thickens and actually becomes a barrier for topical therapy. This review discusses novel antimicrobial treatment strategies based on drug delivery systems (DDS) for AOM. To deliver drugs enough to kill the pathogenic bacteria without systemic side effects, the development of new antimicrobial treatment strategy applying innovative drug DDS has been expected. The sustained-release DDS can achieve sufficient time for antimicrobial concentrations to exceed minimum inhibitory concentration (MIC) for time-dependent antibiotics as well as enough maximum concentration for dose-dependent antibiotics to eradicate causative pathogens in the middle ear. The development of trans-tympanic membranes of DDS, such as hydrogels with chemical permeation enhancers (CPEs), is another attractive strategy. Phage is a promising strategy for developing DDS-based therapies. The DDS formulations enable antimicrobial treatment of AOM by a single dose and thus, an attractive future antimicrobial treatment for AOM.

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High concentrations of middle ear antimicrobial peptides and proteins and proinflammatory cytokines are associated with detection of middle ear pathogens in children with recurrent acute otitis media

Cited by 10 publications

References 52 publications

Innate Immunity in the Middle Ear Mucosa

Innate Immunity in the Middle Ear Mucosa

An Update on Antimicrobial Peptides (AMPs) and Their Delivery Strategies for Wound Infections

Novel Antimicrobial Treatment Strategy Based on Drug Delivery Systems for Acute Otitis Media

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