Assessment of Inhalation Exposures to Indoor and Occupational Aerosols - Murine Models of Repeated Fungal Inhalation Exposure

National Institute Of Environmental Health Sciences

Investigators

Abstract

Adverse health effects have been associated with microbial growth and damp indoor environments; however, the mechanisms of toxicity associated with fungal exposure remain understudied. Mold was nominated to the NTP for toxicological characterization and based on available methodologies and expertise, NIOSH was identified as a collaborator to conduct sub-chronic inhalation exposures studies with NTP-nominated fungal species. A computer-controlled acoustical generator system (AGS), based on a modified acoustically powered particle (Pitt-3) generator, was utilized for these studies, and models a natural human exposure that could be encountered in a fungal contaminated environment. The studies conducted under this subproject characterize the toxicological and pulmonary immune responses associated with repeated fungal exposure. These studies are separated into two phases ? the first phase characterizing the cultivation and aerosol optimization of the targeted fungal species and the second phase consisting of 13-week in vivo exposure studies. In FY21, NTP published the report for the 13-week studies conducted to examine toxicity following exposure to Aspergillus fumigatus. NTP received the final report from NIOSH on 13-week exposure studies for Stachybotrys chartarum, and the NTP report is in preparation. Studies assessing the pulmonary and systemic toxicity following repeated inhalation exposure to Aspergillus versicolor began in 2021. Preliminary studies indicate increases in cells and circulating cytokines associated with the innate immune response early in the exposure period, which shifted to a T helper 2 driven response at later time points. Similar to the reported responses following A. fumigatus and S. chartarum exposure, preliminary data revealed pulmonary arterial tissue remodeling following repeated subchronic exposure to A. versicolor, highlighting the potential for cardiovascular involvement in human fungal exposures. The analysis of miRNA, mRNA, and proteomic datasets derived from the lung homogenates of viable, nonviable, and air-only control samples is ongoing.