STAT1 deficiency predisposes to spontaneous otitis media

Abstract

Signal transducer and activator of transcription 1 (STAT1) is known to be an important player in inflammatory responses. STAT1 as a transcription factor regulates the expression of multiple proinflammatory genes. Inflammatory response is one of the common effects of ototoxicity. Our group reported that hair cells of STAT1 knockout (STAT1-KO) mice are less sensitive to ototoxic agents in-vitro. The effect of inflammatory responses in STAT1-KO mice has primarily been studied challenging them with several pathogens and analyzing different organs of those mice. However, the effect of STAT1 ablation in the mouse inner ear has not been reported. Therefore, we evaluated the cochlear function of wild type and STAT1-KO mice via auditory brain stem response (ABR) and performed histopathologic analysis of their temporal bones. We found ABR responses were affected in STAT1-KO mice with cases of bilateral and unilateral hearing impairment. Histopathologic examination of the middle and inner ears showed bilateral and unilateral otitis media. Otitis media was characterized by effusion of middle and inner ear that varied between the mice in volume and inflammatory cell content. In addition, the thickness of the middle ear mucosae in STAT1-KO mice were more pronounced than those in wild type mice. The degree of middle and inner ear inflammation correlated with ABR threshold elevation in STAT1-KO mice. It appears that a number of mice with inflammation underwent spontaneous resolution. The ABR thresholds were variable and showed a tendency to increase in homozygous and heterozygous STAT1-KO mice. These findings suggest that STAT1 ablation confers an increased susceptibility to otitis media leading to hearing impairment. Thus, the study supports the new role of STAT1 as otitis media predisposition gene.

CD4 T-cell depletion prevents Lassa fever associated hearing loss in the mouse model

“…Our histopathology studies showed significant damage to the neural and vascular structures in the cochlea of the LASV infected mice. There is a clear difference to the reported spontaneous middle ear infection in Stat1-KO mice with no apparent pathology in the cochlea [ 23 ].…”

“…The Stat1-KO mice are known to develop middle ear infection spontaneously around 12–13 weeks of age resulting in unilateral or bilateral conductive hearing loss, which resolves in several weeks [ 23 ]. At the onset of hearing loss at 3 w.p.i., our Stat1-KO mice were around the susceptible age for developing middle ear infections.…”

Proteomic Study of Middle Ear Effusion and Its Clinical Application for Otitis Media with Effusion

“…Tumor necrosis factor-alpha (TNF-a), various kinds of interleukin and other immune factors have been studied. 15 , 16 Additionally, CD4+ T cells and CD8+ T cells have been investigated as immune cell markers in OME. 17 …”

“…Tumor necrosis factor-alpha (TNF-a), various kinds of interleukin and other immune factors have been studied. 15,16 Additionally, CD4+ T cells and CD8+ T cells have been investigated as immune cell markers in OME. 17 These various lines of research contribute to our understanding of the multifactorial nature of OME, involving factors such as bacterial infection, inflammatory responses, radiotherapy-related changes, and allergic processes.…”

Pharmacological Effects of Polyphenol Phytochemicals on the JAK-STAT Signaling Pathway

“…Under normal physiological conditions, the STAT protein exists in the cytoplasm in an inactive form or is briefly activated (Bodmer et al, 2020). A variety of cytokines attach to type I/II cytokine receptors to dimerize the receptors.…”