Toll-like receptor 9 partially regulates lung inflammation induced following exposure to chicken barn air

作者：Schneberger David; Aulakh Gurpreet; Channabasappa Shankaramurthy; Singh Baljit^*

来源：Journal of Occupational Medicine and Toxicology, 2016, 11(1): 31.

DOI：10.1186/s12995-016-0121-x

• Barn dust
• TLR9
• CpG DNA
• Macrophages
• Neutrophils
• BAL

Background: Exposure to animal barn air is an occupational hazard that causes lung dysfunction in barn workers. Respiratory symptoms experienced by workers are typically associated with endotoxin and TLR4 signalling, but within these environments gram negative bacteria constitute only a portion of the total microbial population. In contrast, unmethylated DNA can be found in all bacteria, some viruses, and mold. We hypothesized that in such environments TLR9, which binds unmethylated DNA, contributes to the overall immune responses in the lung.
Methods: Using a mouse model, wild-type and TLR9(-/-) mice were exposed to chicken barn air for 1, 5, or 20 days. Blood serum and bronchiolar lavage fluid was tested against a panel of six TLR9-induced cytokines (IL-1 beta, IL-6, IL-10, IL-12, TNF alpha, and IFN gamma) for changes in expression. Bronchiolar lavage fluid (BAL) was also tested for macrophage as well as monocyte migration.
Results: There were significant decreases in serum TNF alpha after a single day exposure in TLR9(-/)- mice. BAL concentrations of TNF alpha and IFN gamma, as well as TNF alpha in serum in TLR9(-/-) mice were also reduced after barn exposure for 5 days. After 20 days of exposure IFN gamma was significantly reduced in lavage of TLR9(-/-) mice. Myeloperoxidase (MPO) accumulation in the lung was reduced at 20 days of exposure in TLR9(-/-) mice, as was total lavage cell counts. However, Masson's staining revealed no apparent lung histological differences between any of the treatment groups.
Conclusions: Taken together our data show TLR9 plays a partial role in lung inflammation induced following exposure to chicken barn air potentially through binding of unmethylated DNA.

• 出版日期2016-7-1