Immunomodulatory Response of the Middle Ear Epithelial Cells in Otitis Media

Abstract

Hypothesis The middle ear (ME) epithelium transforms because of changed immunomodulation during infection. Introduction The epithelial cells of the tympanic cavity represent the first line of defense in the context of otitis media. They can convert from a typical mucosal site into a respiratory epithelium and vice versa. Our goal is to depict the specific immune response of epithelial cells after infection at the molecular level. Methods The investigations were carried out on healthy and inflamed ME tissue, removed during surgical interventions in mouse and human models, and in a human in-vitro cell model in human ME epithelial cell line. We determined the epithelial localization of the protein expression of Toll- and NOD-like immune receptors and their associated signaling molecules using immunohistochemistry. In addition, we examined growth behavior and gene expression due to direct stimulation and inhibition. Results We found clinically and immunobiologically confirmed transformation of the inflamed ME epithelium depending on their origin, as well as differences in the distribution of Toll-like receptors and nucleotide-binding oligomerization domain-like receptors in the epithelial cell lining. Dysregulated gene and protein expression of the inflammatory and apoptotic genes could be modulated by stimulation and inhibition in the epithelial cells. Conclusions The local ME mucosal tissue is believed to modulate downstream immune activity after pathogen invasion via intrinsic cellular mechanism. Using translation approaches to target these molecular pathways may offer more reliable clinical resolution of otitis media in the future.

1,8-Cineol Attenuates Checkpoint Molecule PDL-1 and Adhesion Molecule CX3CR1 in Circulating Monocytes in Otitis Media Patients

“…Chronic otitis media is closely associated with distinct inflammatory processes within the middle ear in response to different bacterial and viral infections, as well as with the immunomodulatory response of the middle ear epithelial cells [ 9 , 34 , 35 ]. The role of CXCL10 in otitis media has hardly been investigated so far.…”