Development of a Corticosteroid-Immunosuppressed Mouse Model to Study the Pathogenesis and Therapy of Influenza-Associated Pulmonary Aspergillosis

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 a...

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Bibliographic Details
Published in:The Journal of infectious diseases 2023-04, Vol.227 (7), p.901-906
Main 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
Format: Article
Language:English
Subjects:
Acetic acid
Adrenal Cortex Hormones - therapeutic use
Amphotericin B
Animals
Antifungal agents
Antifungal Agents - therapeutic use
Antiviral agents
Antiviral drugs
Aspergillosis
Aspergillosis - drug therapy
Aspergillus fumigatus
Corticosteroids
Humans
Immunosuppression
Influenza
Influenza, Human - complications
Influenza, Human - drug therapy
Inoculum
Mice
Morbidity
Oseltamivir
Pathogenesis
Pulmonary Aspergillosis - complications
Pulmonary Aspergillosis - drug therapy
Tracheobronchitis
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Summary: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. 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.
ISSN:0022-1899
1537-6613
DOI:10.1093/infdis/jiad001