N-acetylcysteine is associated with restoration of autophagy-related signaling and reduced intracellular Mycobacterium avium in alveolar type 1 epithelial cells.

PURPOSE: In patients with pulmonary Mycobacterium avium complex disease, the barrier function of the airway epithelium is reduced. In this study, we focused on the host defense responses of alveolar epithelial cells to M. avium.

METHODS AND

RESULTS

Clinical isolates of M. avium were used to infect murine alveolar type 1 epithelial cells (AT1s). Administration of N-acetylcysteine suppressed bacterial growth in the infected cells. Expression of the autophagosome marker microtubule-associated protein 1 light chain 3 was decreased in M. avium-infected cells and appeared to be restored by N-acetylcysteine administration. M. avium infection negatively affected the autophagic pathway, specifically mTORC1 signaling and its upstream factor, SLC37A4, which was partially restored by N-acetylcysteine administration. Autophagy inhibition by bafilomycin attenuated the NAC-associated reduction in bacterial load, suggesting involvement of autophagy-related pathways.

CONCLUSIONS

Our results suggest that M. avium infection is associated with suppressed autophagy-related responses in AT1s. NAC may function as an immunomodulatory agent by modulating autophagy-associated pathways and reducing intracellular bacterial burden.