Development and Characterization Of a Murine Model Of Repeated Dry Exposure To Aerosolized Fungal Conidia

Dr. Ajay Nayak, PhD, Dr. Amanda Buskirk, PhD, Mr. W.Travis Goldsmith, Ms. Angela Lemons, Dr. Justin Hettick, PhD, Dr. Michael Kashon, PhD, Ms. Amy Cumpston, Mr. Jared Cumpston, Mr. Howard Leonard, Mr. Walter McKinney, Dr. David Frazer, PhD, Dr. Donald H. Beezhold, PhD, FAAAAI, Dr. Brett J. Green, PhD

Abstract: 

Rationale

Personal fungal exposures are associated with a variety of adverse health outcomes, including invasive disease, allergic sensitization, and asthma. Most murine models of fungal exposure have utilized aspiration or inhalation of uncharacterized extracts or liquid conidial suspensions that do not resemble natural human exposures. These studies were conducted to characterize a novel dry aerosol repeated exposure model toAspergillus fumigatus with a goal towards defining the resulting immune response.

 

Methods

In these studies, immunocompetent Balb/c mice were repeatedly exposed to A. fumigatus wild-type (WT) or melanin-deficient (Δalb1) conidia via aerosol exposure of dry conidia using an acoustical generator. Flow cytometric and histopathologic analyses were conducted to characterize the immune responses and the associated lung pathology following repeated exposures.

 

Results

Histological analysis demonstrated in vivo germination in mice exposed to A. fumigatus conidia. WT exposure led to increased numbers of adaptive immune system cells (B cells and T cells) and innate immune effector cells (eosinophils, neutrophils, and macrophages). Importantly, CD8+IL-17+ (Tc17) cells were also elevated in exposed mice, which appeared to closely correlate with the germination of WT A. fumigatus conidia.

 

Conclusions

The data presented here are among the first to characterize the immune responses to repeated dry fungal exposures in immunocompetent animals. Dry aerosol exposures via the acoustical generator may provide more accurate analyses of immune responses following exposures to other environmentally prevalent fungi.

abstract No: 

351
    • AAAAI 2014 (70th)