Optimization of Aspergillus versicolor Culture and Aerosolization in a Murine Model of Inhalational Fungal Exposure

Author:

Blackwood Catherine B.1ORCID,Croston Tara L.1,Barnes Mark A.1,Lemons Angela R.1ORCID,Rush Rachael E.1,Goldsmith Travis1ORCID,McKinney Walter G.1ORCID,Anderson Stacey1,Weaver Kelly L.2ORCID,Sulyok Michael3ORCID,Park Ju-Hyeong4,Germolec Dori5,Beezhold Donald H.16,Green Brett16

Affiliation:

1. Allergy and Clinical Immunology Branch, Health Effects Laboratory Division, National Institute for Occupational Safety and Health, Centers for Disease Control and Prevention, Morgantown, WV 26505, USA

2. Department of Pharmacology & Toxicology, Indiana University School of Medicine, Indianapolis, IN 46202, USA

3. Department of Agrobiotechnology (IFA-Tulln), Institute of Bioanalytics and Agro-Metabolomics, University of Natural Resources and Life Sciences, 1180 Vienna, Austria

4. Respiratory Health Division, National Institute for Occupational Safety and Health, Centers for Disease Control and Prevention, Morgantown, WV 26505, USA

5. Division of Translational Toxicology, National Institute of Environmental Health Sciences, Research Triangle Park, NC 27709, USA

6. Office of the Director, Health Effects Laboratory Division, National Institute for Occupational Safety and Health, Centers for Disease Control and Prevention, Morgantown, WV 26505, USA

Abstract

Aspergillus versicolor is ubiquitous in the environment and is particularly abundant in damp indoor spaces. Exposure to Aspergillus species, as well as other environmental fungi, has been linked to respiratory health outcomes, including asthma, allergy, and even local or disseminated infection. However, the pulmonary immunological mechanisms associated with repeated exposure to A. versicolor have remained relatively uncharacterized. Here, A. versicolor was cultured and desiccated on rice then placed in an acoustical generator system to achieve aerosolization. Mice were challenged with titrated doses of aerosolized conidia to examine deposition, lymphoproliferative properties, and immunotoxicological response to repeated inhalation exposures. The necessary dose to induce lymphoproliferation was identified, but not infection-like pathology. Further, it was determined that the dose was able to initiate localized immune responses. The data presented in this study demonstrate an optimized and reproducible method for delivering A. versicolor conidia to rodents via nose-only inhalation. Additionally, the feasibility of a long-term repeated exposure study was established. This experimental protocol can be used in future studies to investigate the physiological effects of repeated pulmonary exposure to fungal conidia utilizing a practical and relevant mode of delivery. In total, these data constitute an important foundation for subsequent research in the field.

Funder

NIOSH

Publisher

MDPI AG

Subject

Plant Science,Ecology, Evolution, Behavior and Systematics,Microbiology (medical)

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