Immunohistochemical Distribution of Extracellular Matrix Components and Keratin in Experimentally Induced Otitis Media

Abstract

The distribution of collagen types I, III, and IV and of laminin, fibronectin, and keratin was studied in otitis media experimentally induced by Streptococcus pneumoniae in the chinchilla. The expression of interstitial collagen types I and III and of fibronectin was increased in the subepithelial space that was thickened by inflammation in the acute period of infection. The expression of collagen type IV in the subepithelial space could be seen in the early period. The epithelial cells in the middle ear changed from flat cuboidal to pseudostratified columnar in pneumococcus-inoculated ears, and the number of keratin-positive epithelial cells in the middle ear increased remarkably after infection. These results indicate that changes in epithelial cell differentiation effected by the extracellular matrix correlate with changes in expression of keratin. It is proposed that the extracellular matrix may contribute to tissue repair in the middle ear after bacterial infection by interfering with cell proliferation of epithelial cells and fibroblasts.

TLR4-mediated induction of TLR2 signaling is critical in the pathogenesis and resolution of otitis media

“…These results suggest that both TLR2 and TLR4 are essential to a timely recovery from non-typeable H. influenzae -induced otitis media. Toll-like receptor-2 appears most critical for the later clearance of neutrophils from the middle ear and for complete elimination of bacteria, and TLR4 appears to be more important for priming and mounting the initial host response through contact with bacterial pathogen associated molecular patterns and perhaps through exposure to various potential endogenous ligands for the TLR family 33 that are present in the middle ear, such as hyaluronic acid, 34 fibronectin 35,36 surfactant, 37 heat shock protein 70, 34 heparan sulfate, 38 and defensins 1 and 2. 39 Indeed, we found slightly higher basal levels of TNF gene induction in TLR4 −/− mice than in TLR2 −/− or wild-type mice.…”