The Bordetella type III secretion system effector BteA targets host eosinophil-epithelial signaling to promote IL-1Ra expression and persistence

Eosinophils are traditionally associated with parasitic infections and allergic pathologies. However, emerging evidence highlights their underappreciated roles during mucosal bacterial infections. Using in vivo and in vitro approaches, we demonstrate that classical Bordetella spp. increase IL-1Ra production from both epithelial cells and eosinophils to facilitate immune evasion and persistence. Depletion of IL-1Ra via genetic knockout or antibody neutralization in vivo accelerated bacterial clearance. We show that the Bordetella type III secretion system (T3SS) effector, BteA, promotes AkT/mTOR pathway activation leading to IL-1Ra expression, which is independent of IL-1α or IL-1β production. Together, our findings uncover the molecular mechanism by which classical Bordetellae exploit host epithelial-eosinophil signaling to exclusively upregulate IL-1Ra and dampen host inflammation for persistence. These results provide therapeutic targets for controlling disease caused by long-term Bordetella infection and may have broader applications for other respiratory pathogens. Moreover, these insights expand our understanding of eosinophil function beyond traditional paradigms.