Innate Immunity and the Role of Defensins in Otitis Media

Underwood, Mark A.

doi:10.1007/s11882-011-0223-6

Cited by 24 publications

(20 citation statements)

References 73 publications

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“…They also identify the resting ME cells that express major determinants of innate immunity. As noted above, innate immunity is responsible for the normal resolution of OM (e.g., Underwood and Bakaletz, 2011;Kurabi et al, 2016). The immediate response provided by the cell of the normal ME is critical to initiating this first line of defense against infection.…”

Section: Discussionmentioning

confidence: 99%

Single-Cell Transcriptomes Reveal a Complex Cellular Landscape in the Middle Ear and Differential Capacities for Acute Response to Infection

et al. 2020

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Single-cell transcriptomics was used to profile cells of the normal murine middle ear. Clustering analysis of 6770 transcriptomes identified 17 cell clusters corresponding to distinct cell types: five epithelial, three stromal, three lymphocyte, two monocyte, two endothelial, one pericyte and one melanocyte cluster. Within some clusters, cell subtypes were identified. While many corresponded to those cell types known from prior studies, several novel types or subtypes were noted. The results indicate unexpected cellular diversity within the resting middle ear mucosa. The resolution of uncomplicated, acute, otitis media is too rapid for cognate immunity to play a major role. Thus innate immunity is likely responsible for normal recovery from middle ear infection. The need for rapid response to pathogens suggests that innate immune genes may be constitutively expressed by middle ear cells. We therefore assessed expression of innate immune genes across all cell types, to evaluate potential for rapid responses to middle ear infection. Resident monocytes/macrophages expressed the most such genes, including pathogen receptors, cytokines, chemokines and chemokine receptors. Other cell types displayed distinct innate immune gene profiles. Epithelial cells preferentially expressed pathogen receptors, bactericidal peptides and mucins. Stromal and endothelial cells expressed pathogen receptors. Pericytes expressed pro-inflammatory cytokines. Lymphocytes expressed chemokine receptors and antimicrobials. The results suggest that tissue monocytes, including macrophages, are the master regulators of the immediate middle ear response to infection, but that virtually all cell types act in concert to mount a defense against pathogens.

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Section: Discussionmentioning

confidence: 99%

Single-Cell Transcriptomes Reveal a Complex Cellular Landscape in the Middle Ear and Differential Capacities for Acute Response to Infection

et al. 2020

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“…It has been shown that TNF-αcan modulate the expression of Toll-like receptors (TLR) and is also essential for TLR signaling, including nuclear factor (NF)-κB, via both positive [7] and negative [8] feedback mechanisms. Recent data illustrate a critical role for TLR2 and TLR4 signaling via a MyD88-dependent pathway in the middle ear inflammatory responses to bacteria, and they are particularly important during the recovery process from OM [9]. Thus, MIF can indirectly trigger inflammatory responses in OM through TNF-α.…”

Section: Introductionmentioning

confidence: 99%

Blocking macrophage migration inhibitory factor activity alleviates mouse acute otitis media in vivo

Zhang

Zheng

et al. 2014

Immunology Letters

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This study was to investigate the role of macrophage migration inhibitory factor (MIF) in mouse acute otitis media (AOM), we hypothesize that blocking MIF activity will relieve mouse AOM. A mouse AOM model was constructed by injecting lipopolysaccharide (LPS) into the middle ear of C57BL/6 mice through the tympanic membrane (TM). MIF levels were measured by real-time PCR (RT-PCR) and ELISA after LPS application. Normal or AOM mice were given PBS or ISO-1 (MIF antagonist) every day for 10 days and the hearing levels were determined by measuring auditory brainstem response (ABR) threshold. After the ABR test finished, H&E staining was conducted and the inflammation was also measured by detecting interleukin (IL)-1β, tumor necrosis factor (TNF)-α and vascular endothelial growth factor (VEGF) levels with RT-PCR and ELISA. TLR-4 expression was determined by western blotting and NF-κB activation was determined by electrophoretic mobility shift assays. Compared with the normal control, MIF levels in the middle ear of LPS-induced AOM mice were significant increased. The ABR results showed that mean ABR thresholds in ISO-1 treated AOM mice were significantly reduced compared with PBS treated AOM mice since day 7, indicating that ISO-1 treatment potentially improved the hearing levels of AOM mice. H&Estaining showed that ISO-1 treatment could reduce the mucosal thickness of AOM mice. In ISO-1 treated mice, TLR-4 expression and levels of IL-1β, TNF-α and VEGF were significantly lower compared with PBS treated AOM mice. ISO-1 treatment also significantly inhibited NF-κB activation in AOM mice compared with PBS treated AOM mice. These results suggested that blocking the activity of MIF by ISO-1 could reduce the inflammation in AOM mice in which process TLR-4 and NF-κB were involved. The reduction in MIF activity is conducive to alleviate mouse AOM, which may serve as a potential therapeutic target for the treatment of AOM.

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“…These genes encode peptides or proteins that are involved in host defense against bacterial infection, and the down-regulation in co-treatment indicates that the host defense was decreased. Defensins are broad-spectrum antimicrobial peptides that have been implicated in prevention of AOM (Underwood and Bakaletz, 2011). It was reported that deficiency of S100A8/A9 in mice could promote the progression of pneumonia caused by bacterial infection (Achouiti et al, 2015).…”

Section: Discussionmentioning

confidence: 99%

Asian Sand Dust Particles Increased Pneumococcal Biofilm Formation in vitro and Colonization in Human Middle Ear Epithelial Cells and Rat Middle Ear Mucosa

Yadav

Chae

et al. 2020

Front. Genet.

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Introduction: Air pollutants such as Asian sand dust (ASD) and Streptococcus pneumoniae are risk factors for otitis media (OM). In this study, we evaluate the role of ASD in pneumococcal in vitro biofilm growth and colonization on human middle ear epithelium cells (HMEECs) and rat middle ear using the rat OM model. Methods: S. pneumoniae D39 in vitro biofilm growth in the presence of ASD (50-300 µg/ml) was evaluated in metal ion-free BHI medium using CV-microplate assay, colony-forming unit (cfu) counts, resazurin staining, scanning electron microscopy (SEM), and confocal microscopy (CF). Biofilm gene expression analysis was performed using real-time RT-PCR. The effects of ASD or S. pneumoniae individually or on cotreatment on HMEECs were evaluated by detecting HMEEC viability, apoptosis, and reactive oxygen species (ROS) production. In vivo colonization of S. pneumoniae in the presence of ASD was evaluated using the rat OM model, and RNA-Seq was used to evaluate the alterations in gene expression in rat middle ear mucosa. Results: S. pneumoniae biofilm growth was significantly (P < 0.05) elevated in the presence of ASD. SEM and CF analysis revealed thick and organized pneumococcal biofilms in the presence of ASD (300 µg/ml). However, in the absence of ASD, bacteria were unable to form organized biofilms, the cell size was smaller than normal, and long chain-like structures were formed. Biofilms grown in the presence of ASD showed elevated expression levels of genes involved in biofilm formation (luxS), competence (comA, comB, ciaR), and toxin production (lytA and ply). Prior exposure of HMEECs to ASD, followed by treatment for pneumococci, significantly (P < 0.05) decreased cell viability and increased apoptosis, and ROS production. In vivo experiment results showed significantly (P < 0.05) more than 65% increased bacteria colonization in rat middle ear mucosa in the presence of ASD. The apoptosis, cell death, DNA repair,

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Innate Immunity and the Role of Defensins in Otitis Media

Cited by 24 publications

References 73 publications

Single-Cell Transcriptomes Reveal a Complex Cellular Landscape in the Middle Ear and Differential Capacities for Acute Response to Infection

Single-Cell Transcriptomes Reveal a Complex Cellular Landscape in the Middle Ear and Differential Capacities for Acute Response to Infection

Blocking macrophage migration inhibitory factor activity alleviates mouse acute otitis media in vivo

Asian Sand Dust Particles Increased Pneumococcal Biofilm Formation in vitro and Colonization in Human Middle Ear Epithelial Cells and Rat Middle Ear Mucosa

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