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.

Department of Biochemistry Purdue University West Lafayette IN USA

Department of Biological Sciences Purdue University West Lafayette IN USA

Department of Microbiology and Immunology Louisiana State University Health Sciences Center at Shreveport Shreveport LA USA

Department of Microbiology and Immunology University of Maryland School of Medicine Baltimore MD USA

Department of Pediatrics University of Cincinnati College of Medicine Cincinnati OH USA

Division of Allergy and Immunology Cincinnati Children's Hospital Medical Center Cincinnati OH USA

Laboratory of Infection Biology Institute of Microbiology of the Czech Academy of Sciences Prague Czech Republic

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