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Innate signaling in otitis media: pathogenesis and recovery.

Leichtle A, Lai Y, Wollenberg B, Wasserman SI, Ryan AF - Curr Allergy Asthma Rep (2011)

Bottom Line: We review recent research that has advanced our understanding of how innate immunity in the middle ear is mediated by the interaction of pathogen molecules with receptors such as the TLRs, leading to the activation of adaptor molecules and production of proinflammatory cytokines.TLR genes and signaling molecules are upregulated in OM in a murine model.It is concluded that an intact innate immune signaling system is critical to recovery from bacterial OM.

View Article: PubMed Central - PubMed

Affiliation: Department of Otolaryngology, University of Lübeck, Ratzeburger Allee 160, 23564, Lübeck, Germany. anke.leichtle@uk-sh.de

ABSTRACT
Otitis media (OM) is the most prevalent childhood disease in developed countries. Involvement of innate immunity mediated by Toll-like receptors (TLRs) in OM has been implicated primarily in cell lines and by association studies of innate immune gene polymorphisms with OM prevalence. However, the precise role of innate immunity in OM is incompletely understood. We review recent research that has advanced our understanding of how innate immunity in the middle ear is mediated by the interaction of pathogen molecules with receptors such as the TLRs, leading to the activation of adaptor molecules and production of proinflammatory cytokines. TLR genes and signaling molecules are upregulated in OM in a murine model. Deletion of several key innate immune genes results in persistent OM in mice, coupled with an inability to clear bacterial infection from the middle ear. It is concluded that an intact innate immune signaling system is critical to recovery from bacterial OM.

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A quantitative evaluation of mucosal thickness in the middle ear cavity throughout the course of otitis media. Mucosal thickness is greater in mice lacking key Toll-like receptor (TLR) signaling genes than in wild-type (WT) mice (n = 6–8 middle ears per time point). Bars represent the mean ± SEM. aSignificantly different from WT (P < 0.05). MyD88—myeloid differentiation factor-88; NTHi—nontypeable Haemophilus influenzae; TRIF—Toll/interleukin-1 receptor domain containing adaptor inducing interferon-β
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Fig1: A quantitative evaluation of mucosal thickness in the middle ear cavity throughout the course of otitis media. Mucosal thickness is greater in mice lacking key Toll-like receptor (TLR) signaling genes than in wild-type (WT) mice (n = 6–8 middle ears per time point). Bars represent the mean ± SEM. aSignificantly different from WT (P < 0.05). MyD88—myeloid differentiation factor-88; NTHi—nontypeable Haemophilus influenzae; TRIF—Toll/interleukin-1 receptor domain containing adaptor inducing interferon-β

Mentions: A hallmark of OM is hyperplasia of the middle ear mucosa, which transitions from a single layer of simple squamous epithelial cells and a rudimentary stroma to a pseudostratified respiratory epithelium with extensive stroma during OM [29]. After inoculation of the middle ear with nontypeable H. influenzae, wild-type mice display significant thickening of the middle ear mucosa at day 2 (Fig. 1). Mucosal thickness recovers and the middle ear is histologically normal by day 10. In contrast, while mice with deficiencies in TLR2 or MyD88 initially show similar initial increases in mucosal thickness, the mucosa in such mice continues to increase in thickness and fails to return to normal for at least 3 weeks after inoculation with nontypeable H. influenzae (Fig. 1). Mice deficient in TLR4 or TRIF exhibit more modest delays in mucosal recovery.Fig. 1


Innate signaling in otitis media: pathogenesis and recovery.

Leichtle A, Lai Y, Wollenberg B, Wasserman SI, Ryan AF - Curr Allergy Asthma Rep (2011)

A quantitative evaluation of mucosal thickness in the middle ear cavity throughout the course of otitis media. Mucosal thickness is greater in mice lacking key Toll-like receptor (TLR) signaling genes than in wild-type (WT) mice (n = 6–8 middle ears per time point). Bars represent the mean ± SEM. aSignificantly different from WT (P < 0.05). MyD88—myeloid differentiation factor-88; NTHi—nontypeable Haemophilus influenzae; TRIF—Toll/interleukin-1 receptor domain containing adaptor inducing interferon-β
© Copyright Policy
Related In: Results  -  Collection

Show All Figures
getmorefigures.php?uid=PMC3020300&req=5

Fig1: A quantitative evaluation of mucosal thickness in the middle ear cavity throughout the course of otitis media. Mucosal thickness is greater in mice lacking key Toll-like receptor (TLR) signaling genes than in wild-type (WT) mice (n = 6–8 middle ears per time point). Bars represent the mean ± SEM. aSignificantly different from WT (P < 0.05). MyD88—myeloid differentiation factor-88; NTHi—nontypeable Haemophilus influenzae; TRIF—Toll/interleukin-1 receptor domain containing adaptor inducing interferon-β
Mentions: A hallmark of OM is hyperplasia of the middle ear mucosa, which transitions from a single layer of simple squamous epithelial cells and a rudimentary stroma to a pseudostratified respiratory epithelium with extensive stroma during OM [29]. After inoculation of the middle ear with nontypeable H. influenzae, wild-type mice display significant thickening of the middle ear mucosa at day 2 (Fig. 1). Mucosal thickness recovers and the middle ear is histologically normal by day 10. In contrast, while mice with deficiencies in TLR2 or MyD88 initially show similar initial increases in mucosal thickness, the mucosa in such mice continues to increase in thickness and fails to return to normal for at least 3 weeks after inoculation with nontypeable H. influenzae (Fig. 1). Mice deficient in TLR4 or TRIF exhibit more modest delays in mucosal recovery.Fig. 1

Bottom Line: We review recent research that has advanced our understanding of how innate immunity in the middle ear is mediated by the interaction of pathogen molecules with receptors such as the TLRs, leading to the activation of adaptor molecules and production of proinflammatory cytokines.TLR genes and signaling molecules are upregulated in OM in a murine model.It is concluded that an intact innate immune signaling system is critical to recovery from bacterial OM.

View Article: PubMed Central - PubMed

Affiliation: Department of Otolaryngology, University of Lübeck, Ratzeburger Allee 160, 23564, Lübeck, Germany. anke.leichtle@uk-sh.de

ABSTRACT
Otitis media (OM) is the most prevalent childhood disease in developed countries. Involvement of innate immunity mediated by Toll-like receptors (TLRs) in OM has been implicated primarily in cell lines and by association studies of innate immune gene polymorphisms with OM prevalence. However, the precise role of innate immunity in OM is incompletely understood. We review recent research that has advanced our understanding of how innate immunity in the middle ear is mediated by the interaction of pathogen molecules with receptors such as the TLRs, leading to the activation of adaptor molecules and production of proinflammatory cytokines. TLR genes and signaling molecules are upregulated in OM in a murine model. Deletion of several key innate immune genes results in persistent OM in mice, coupled with an inability to clear bacterial infection from the middle ear. It is concluded that an intact innate immune signaling system is critical to recovery from bacterial OM.

Show MeSH
Related in: MedlinePlus