Development of a Corticosteroid-Immunosuppressed Mouse Model to Study the Pathogenesis and Therapy of Influenza-Associated Pulmonary Aspergillosis. (6th January 2023)

• Record Type: Journal Article
• Authors: Wurster, Sebastian; Pantaleón García, Jezreel; Albert, Nathaniel D; Jiang, Ying; Bhoda, Keerthi; Kulkarni, Vikram V; Wang, Yongxing; Walsh, Thomas J; Evans, Scott; Kontoyiannis, Dimitrios P
• Is Part Of: Journal of infectious diseases. Volume 227:Number 7(2023)
• Page Start: 901
• Page End: 906
• Publication Date: 2023-01-06
• Subjects: pneumonia -- amphotericin B -- aspergillosis -- corticosteroids -- influenza -- mouse model -- oseltamivir; Communicable diseases -- Periodicals; Diseases -- Causes and theories of causation -- Periodicals; Medicine -- Periodicals; Communicable Diseases -- Periodicals; Electronic journals; 616.9
• DOI: 10.1093/infdis/jiad001
• Languages: English
• ISSNs: 0022-1899

Abstract

Abstract: Influenza-associated pulmonary aspergillosis (IAPA) is a feared complication in patients with influenza tracheobronchitis, especially those receiving corticosteroids. Herein, we established 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. Abstract : We established a novel corticosteroid-immunosuppressed murine model of influenza-associated pulmonary aspergillosis (IAPA) that underscores the detrimental effect of corticosteroid therapy on the outcomes of IAPA and provides a preclinical platform to study pathogenesis and therapy of this clinically important entity.