Altered Toll- and Nod-like receptor expression in human middle ear mucosa from patients with chronic middle ear disease

Abstract

Chronic middle ear disease (CMED) appears in different guises like chronic suppurative otitis media and retraction type middle ear disease. A typical feature is recurrent episodes of middle ear infections combined with hearing loss. The mechanisms behind the development of CMED are not fully known. Otitis media with effusion (OME) has for long been regarded as a contributory cause of CMED. There is also a link between frequent episodes of acute otitis media (AOM) and the development of CMED. An aggressive episode of AOM can result in chronic suppurative otitis media with a perforated tympanic membrane.Bacterial colonization of the adenoid is an important risk factor for AOM, and a genetic susceptibility hasbeen revealed for both AOM and OME. 1 Daly K.A. Brown W.M. Segade F. Bowden D.W. Keats B.J. Lindgren B.R. et al. Chronic and recurrent otitis media: a Genome Scan for susceptibility Loci. The American Journal of Human Genetics. 2004; 75: 988-997 Abstract Full Text Full Text PDF PubMed Scopus (66) Google Scholar Most cases of AOM and OME heal spontaneously. This indicates that the middle ear clears itself from infection and inflammation despite the fact that middle ear mucosa is considered to host a limited number of immunocompetent cells. 2 Suenaga S.M.D. Kodama S.M.D. Ueyama S.M.D. Suzuki M.M.D. Mogi G.M.D. Mucosal immunity of the middle ear: analysis at the single cell Level. Laryngoscope. 2001; 111: 290-296 Crossref PubMed Scopus (24) Google Scholar It is likely that local mechanisms might contribute to the protection of the middle ear. In the airways, viruses as well as bacteria induce an innate response by activation of pattern-recognition receptors (PRRs). 3 Bartlett J.A. Fischer A.J. McCray Jr., P.B. Innate immune functions of the airway epithelium. Contributions to Microbiology. 2008; 15: 147-163 Crossref PubMed Scopus (98) Google Scholar Studies in rodent animal models have suggested that this might also be the case for the middle ear. 4 Hirano T. Kodama S. Fujita K. Maeda K. Suzuki M. Role of Toll-like receptor 4 in innate immune responses in a mouse model of acute otitis media. FEMS Immunology & Medical Microbiology. 2007; 49: 75-83 Crossref PubMed Scopus (40) Google Scholar So far, the knowledge about PRRs and other features of innate immunity in the human middle ear is limited. Toll-like receptors (TLRs) are the best characterized PRRs, but recently, another set of PRRs, the Nod-like receptors (NLRs), have emerged. 5 Kumar H. Kawai T. Akira S. Pathogen recognition in the innate immune response. Biochemical Journal. 2009; 420: 1-16 Crossref PubMed Scopus (420) Google Scholar Ten distinct TLRs have to date been described in humans, whereas the NLR family comprises more than 20 members.