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Otitis media induced by peptidoglycan-polysaccharide (PGPS) in TLR2-deficient (Tlr2(-/-)) mice for developing drug
Xiaolin Zhang1, Tihua Zheng2, Lu Sang2
1Transformative Otology and Neuroscience Center, Binzhou Medical University, Yantai 264003, Shandong, PR China; Department of Otolaryngology-HNS, Case Western Reserve University, Cleveland, OH 44106, USA.
Background:
Toll like receptor 2 (TLR2) signaling can regulate the pathogenesis of otitis media (OM). However, the precise role of TLR2 signaling in OM has not been clarified due to the lack of an optimal animal model. Peptidoglycan-polysaccharide (PGPS) of the bacterial cell wall can induce inflammation by activating the TLR2 signaling. This study aimed at examining the pathogenic characteristics of OM induced by PGPS in Tlr2(-/-) mice, and the potential therapeutic effect of sodium aescinate (SA) in this model.
Methods:
Wild-type (WT) and Tlr2(-/-) mice were inoculated with streptococcal PGPS into their middle ears (MEs) and treated intravenously with vehicle or SA daily beginning at 3days prior to PGPS for 6 consecutive days. The pathologic changes of individual mice were evaluated longitudinally.
Results:
In comparison with WT mice, Tlr2(-/-) mice were susceptible to PGPS-induced OM. Tlr2(-/-) mice displayed greater hearing loss, tympanic membrane damage, ME mucosal thickening, longer inflammation state, cilia and goblet cell loss. SA-treatment decreased neutrophil infiltration, modulated TLR2-related gene expression and improved ciliary organization.
Conclusions:
PGPS induced a relatively stable OM in Tlr2(-/-) mice, providing a new model for OM research. Treatment with SA mitigated the pathogenic damage in the ME and may be valuable for intervention of OM.
Insights
Toll-like receptor 2 knockout mice develop stable otitis media (OM) when exposed to peptidoglycan-polysaccharide (PGPS), offering a new model for OM research. Sodium aescinate (SA) treatment effectively reduced inflammation and damage in this model.
Area of Science:
- Immunology
- Otolaryngology
- Microbiology
Background:
- Toll-like receptor 2 (TLR2) signaling influences otitis media (OM) pathogenesis.
- An optimal animal model is lacking to fully understand TLR2's role in OM.
- Bacterial peptidoglycan-polysaccharide (PGPS) activates TLR2 signaling and induces inflammation.
Purpose of the Study:
- To investigate OM pathogenesis induced by PGPS in Tlr2(-/-) mice.
- To evaluate the therapeutic potential of sodium aescinate (SA) in a PGPS-induced OM model.
Main Methods:
- Wild-type (WT) and Tlr2(-/-) mice were used.
- Middle ears (MEs) were inoculated with streptococcal PGPS.
- Mice received daily intravenous treatment with vehicle or SA.
Main Results:
- Tlr2(-/-) mice showed increased susceptibility to PGPS-induced OM compared to WT mice.
- Tlr2(-/-) mice experienced greater hearing loss, tympanic membrane damage, and ME mucosal changes.
- SA treatment reduced neutrophil infiltration, modulated TLR2 gene expression, and improved ciliary organization.
Conclusions:
- PGPS reliably induces OM in Tlr2(-/-) mice, establishing a novel model for OM research.
- SA treatment ameliorates pathogenic damage in the middle ear, suggesting its therapeutic value for OM intervention.
