Multisystem Effects of Mold Inhalation: A Convergence on the Central Nervous System

Abstract

With urbanization, indoor exposure to microbial communities has changed significantly. While indoor bacterial exposure has decreased, indoor fungal exposure has increased. Along with increases in fungal species diversity, indoor air in urbanized countries is characterized by 1,000+ fold differences in mold spore density between buildings. Americans are estimated to spend ~87% of their lives in this new indoor environment, where airborne spore concentrations are unregulated. While the effects of mold exposure on certain respiratory diseases are well established, little is known about how inhaled mold affects extra-respiratory disease. Mold exposure is associated with central nervous system (CNS) symptoms in humans, but very little is known about how mold affects the CNS. Here, I show that subchronic inhalation of a common indoor mold, Aspergillus versicolor, causes neuroinflammatory gene transcription in five out of five brain regions tested, at both 1 and 2 days post inhalation. How peripheral inflammation from mold inhalation causes neuroinflammation is unknown. The mechanisms by which mold is inhaled and cleared implicate the lung, systemic circulation, and gastrointestinal tract as potential areas of immune response. After mold spores are inhaled and deposited in the lung, they are killed by antifungal immunity, cleared from the lung by the mucociliary escalator, swallowed, and excreted through the gastrointestinal tract. Molds produce many mycotoxins which enter enterohepatic recirculation with known toxic effects, including intestinal epithelial disruption. Mycotoxin concentrations in food are regulated in countries comprising ~85% of the world’s population. Inhaled molds produce these same mycotoxins, yet pulmonary exposure is unregulated. The multi-system effects of fungal exposure are poorly understood, and are part of a growing nascent field. Here, I discuss the current state of the indoor fungal environment, known health effects of mold exposure, how fungi activate the immune system, the CNS effects of a common indoor mold, how neuroinflammation from mold exposure might be occurring, future work needed for the systematic analysis of the CNS effects of mold, what is needed to determine the extent to which fungal exposure influences disease, and what might be done to mitigate those effects.