J Infect Dis
. 2023 Jan 6;jiad001.
doi: 10.1093/infdis/jiad001. Online ahead of print.
Development of a corticosteroid-immunosuppressed mouse model to study the pathogenesis and therapy of influenza-associated pulmonary aspergillosis
Sebastian Wurster 1 , Jezreel Pantaleón García 2 , Nathaniel D Albert 1 , Ying Jiang 1 , Keerthi Bhoda 2 , Vikram V Kulkarni 2 , Yongxing Wang 2 , Thomas J Walsh 3 , Scott Evans 2 , Dimitrios P Kontoyiannis 1
Affiliations
- PMID: 36611269
- DOI: 10.1093/infdis/jiad001
Abstract
Influenza-associated pulmonary aspergillosis (IAPA) is a feared complication in patients with influenza tracheobronchitis, especially those receiving corticosteroids. Herein, we establish a novel IAPA mouse model with low-inoculum Aspergillus infection and compared outcomes in mice with and without cortisone acetate (CA) immunosuppression. CA was an independent predictor of increased morbidity/mortality in mice with IAPA. Early antifungal treatment with liposomal amphotericin B was pivotal to improve IAPA outcomes in CA-immunosuppressed mice, even after prior antiviral therapy with oseltamivir. In summary, our model recapitulates key clinical features of IAPA and provides a robust preclinical platform to study the pathogenesis and treatment of IAPA.
Keywords: Pneumonia; amphotericin B; aspergillosis; corticosteroids; influenza; mouse model; oseltamivir.