Pulmonary MicroRNA Expression Profiles Associated with Subchronic Aspergillus fumigatus Exposure

Rationale: The role of small noncoding RNAs involved in pulmonary immune responses to fungi has not been elucidated. The study objective was to evaluate microRNA (miRNAs) profiles in murine lungs and to characterize changes following subchronic exposure to Aspergillus fumigatus spores.

Methods: Three groups (n=3) of naïve female B6C3F1/N mice were exposed via inhalation to viable A. fumigatus conidia (10⁵), nonviable A. fumigatus conidia control (10⁵), or HEPA-filtered air control twice a week for 13 weeks. Total RNA was isolated from whole lung at 24 and 48 hours following the final exposure and sent to Exiqon for miRCURY LNA™ miRNA array analysis, which includes all known miRNAs for mouse registered in miRBASE 18.0. The resultant 415 miRNA dataset was assessed to evaluate the fold changes between viable and control groups.

Results: Approximately 28% and 50% of miRNAs, were altered 24 and 48 hours post-exposure, respectively, when comparing viable to the nonviable and air control groups. MiR-23b-3p, known to regulate genes involved in the IL-13 and IL-33 responses, was identified as having the largest decreased change. MiR-30c-5p and miR-29a-3p, both of which regulate the SMAD2/3 signaling pathway, were also decreased. The miRNAs that demonstrated the largest fold increase included miR-2137 and miR-1947-3p, which are involved in chemokine- and T-cell receptor signaling, respectively.

Conclusions: Examination of the miRNA profile post-fungal exposure demonstrated a large number of altered miRNAs. Our findings support previously reported immune responses following A. fumigatusexposure. Furthermore, altered miRNAs may serve as potential biomarkers to evaluate fungal exposure.