Direct Inoculation of Pathogenic Yeasts into Mouse Lung by Trans-tracheal Instillation.

Abstract

Pathogenic dimorphic fungi are endemic in certain regions and can cause from subclinical infections to systemic mycoses. These pathogens are associated with high mortality and morbidity rates and represent emerging infectious threats to human populations worldwide. Because most fungal pathogens cause lung infection or use the lung as a route to disseminate to other organs, mammalian pulmonary infection models are crucial tools in the advancement of medical mycology. Many different types of animal models of fungal infection have been developed, with murine models being hailed as the gold standard for studies of pathogenesis, to compare virulence between isolates, preclinical evaluation of vaccines and therapies, and host antifungal immune responses. The ability to control numerous variables in performing the model allows for mimicking human disease states and quantitatively monitoring the course of the disease. To model lung inflammation and injury, fungal infectious propagules can be inoculated via intranasal delivery, intratracheal, or aerosolization approaches. The protocol in this chapter details a method for intratracheal delivery of a fungal suspension, where fungal cells are administered directly into the lungs to initiate infection. The aim is to provide a comprehensive description of techniques required to perform mouse pulmonary infection, such that reproducible results are attained, allowing for the use of this in vivo approach for high-quality studies.