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

Authors

Sebastian Wurster
Jezreel Pantaleón García
Nathaniel D Albert
Ying Jiang
Keerthi Bhoda
Vikram V Kulkarni
Yongxing Wang
Thomas J Walsh
Scott Evans
Dimitrios P Kontoyiannis

Publication Date

4-12-2023

Journal

The Journal of Infectious Diseases

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.

Keywords

pneumonia, amphotericin B, aspergillosis, corticosteroids, influenza, mouse model, oseltamivir

DOI

10.1093/infdis/jiad001

PMID

36611269

PMCID

PMC10319956

PubMedCentral® Posted Date

January 2023

PubMedCentral® Full Text Version

Post-print

Published Open-Access

yes