Innate signaling in otitis media: pathogenesis and recovery.
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.
Department of Otolaryngology, University of Lübeck, Ratzeburger Allee 160, 23564, Lübeck, Germany. anke.leichtle@uk-sh.de
Anke
A
Leichtle
Yuping
Y
Lai
Barbara
B
Wollenberg
Stephen I
SI
Wasserman
Allen F
AF
Ryan
D000818:Animals; D002648:Child; D016207:Cytokines / Q000235:genetics / Q000276:immunology / Q000378:metabolism; D006192:Haemophilus Infections / Q000235:genetics / Q000276:immunology / Q000503:physiopathology; D006193:Haemophilus influenzae; D006801:Humans; D007113:Immunity, Innate; D051379:Mice; D010033:Otitis Media / Q000235:genetics / Q000276:immunology* / Q000503:physiopathology; D015398:Signal Transduction / Q000235:genetics / Q000276:immunology; D051195:Toll-Like Receptor 2 / Q000235:genetics / Q000276:immunology / Q000378:metabolism; D051197:Toll-Like Receptor 4 / Q000235:genetics / Q000276:immunology / Q000378:metabolism; D051193:Toll-Like Receptors / Q000235:genetics / Q000276:immunology* / Q000378:metabolism; D014409:Tumor Necrosis Factor-alpha / Q000235:genetics / Q000276:immunology / Q000378:metabolism
D016207:Cytokines; C495342:TLR2 protein, human; C495345:TLR4 protein, human; D051195:Toll-Like Receptor 2; D051197:Toll-Like Receptor 4; D051193:Toll-Like Receptors; D014409:Tumor Necrosis Factor-alpha