Immunomodulatory effects of bacterial lysates on the IL-17 signaling pathway in an asthma mouse model

Severe asthma is a clinically heterogeneous and often treatment-refractory condition, in which steroid resistance and persistent neutrophilic airway inflammation are frequently driven by the IL-17 signaling axis. However, upstream regulatory mechanisms and effective therapeutic interventions targeting this pathway remain poorly defined. This study aimed to investigate the immunomodulatory effects of OM-85, a bacterial lysate-based agent, and its regulatory role on IL-17-associated signaling in a murine model of allergic asthma.

An ovalbumin (OVA)-induced mouse model of asthma was used to evaluate the effects of OM-85. Airway hyperresponsiveness (AHR), histopathological changes, and cytokine profiles were assessed. Quantitative real-time PCR and western blotting were performed to evaluate inflammatory gene and protein expression. Transcriptomic enrichment and immunofluorescence co-localization analyses were conducted to validate OM-85's impact on the IL-17A/TRAF5/NF-κB signaling pathway.

OM-85 administration significantly reduced AHR, goblet cell hyperplasia, and peribronchial collagen deposition in asthmatic mice. Expression of Th2 cytokines (IL-4, IL-5, and IL-13) was markedly suppressed, while IFN-γ levels were restored, indicating a rebalancing of Th1/Th2 responses. Bioinformatics analysis and experimental validation revealed that OM-85 downregulated the IL-17A/TRAF5/NF-κB axis. Immunofluorescence staining confirmed a reduction in IL-17A-Ly6G and IL-17A-TRAF5co-localization, suggesting disruption of IL-TRAF-mediated inflammatory circuits.

OM-85 exerts multi-dimensional immunoregulatory effects in allergic asthma by suppressing IL-17A-mediated signaling and restoring immune homeostasis. These findings suggest that OM-85 may represent a promising immunotherapeutic approach for managing steroid-resistant asthma phenotypes associated with IL-17-driven inflammation.