Continuous Inhalation Exposure to Fungal Allergen Particulates Induces Lung Inflammation While Reducing Innate Immune...

Area of Science:

• Environmental toxicology
• Neuroimmunology
• Respiratory medicine

Background:

• Fine and ultrafine particulates can trigger inflammatory responses in the lung and brain.
• Inhalation is a common exposure route for toxicants, while allergens are often studied via intranasal or injection routes.
• Alternaria alternata is a common fungal allergen linked to asthma.

Purpose of the Study:

• To investigate if continuous inhalation of aerosolized Alternaria alternata particulates induces innate inflammatory responses in the lung and brain.
• To assess the impact of fungal allergen inhalation on the central nervous system, particularly the respiratory control circuits.

Main Methods:

• Adult mice were continuously exposed to aerosolized ultrafine Alternaria alternata particulates for 96 hours in a controlled environmental chamber.
• Quantitative polymerase chain reaction (qPCR) and flow cytometry were used to analyze immune responses in whole brain and brainstem samples.
• Histologic analysis examined immunoreactivity of Iba1 and glial fibrillary acidic protein (GFAP) in brainstem and hippocampus.

Main Results:

• Lung inflammation was induced, but whole brain samples showed no detectable innate immune response.
• Significant decreases in Arginase 1, inducible nitric oxide synthase (iNOS), and tumor necrosis factor alpha (TNF-α) mRNA were observed in brainstem samples.
• A reduction in Toll-like receptor 2 (TLR2)-expressing microglia and Iba1 immunoreactivity was detected in the brainstem and hippocampus.

Conclusions:

• Inhalation of fungal allergen particulates sufficient to cause lung inflammation surprisingly reduces baseline expression of certain innate immune molecules in the brainstem.
• These findings suggest a potential link between inhaled natural allergens and altered neuroimmune function in the central nervous system's respiratory control regions.
• The observed reductions in immune molecules resemble endotoxin tolerance, indicating a complex neuroinflammatory response to inhaled allergens.