title: Toll-like receptor 9 partially regulates lung inflammation induced following exposure to chicken barn air.
abstract: 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-1β, IL-6, IL-10, IL-12, TNFα, and IFNγ) 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 TNFα after a single day exposure in TLR9(-/-) mice. BAL concentrations of TNFα and IFNγ, as well as TNFα in serum in TLR9(-/-) mice were also reduced after barn exposure for 5 days. After 20 days of exposure IFNγ 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.
authors.affiliation: Department of Veterinary Biomedical Sciences, Western College of Veterinary Medicine, University of Saskatchewan, 52 Campus Drive, Saskatoon, SK S7N 5B4 Canada.
authors.forename: David
authors.initials: D
authors.lastname: Schneberger
authors.affiliation: Department of Veterinary Biomedical Sciences, Western College of Veterinary Medicine, University of Saskatchewan, 52 Campus Drive, Saskatoon, SK S7N 5B4 Canada.
authors.forename: Gurpreet
authors.initials: G
authors.lastname: Aulakh
authors.affiliation: Department of Veterinary Biomedical Sciences, Western College of Veterinary Medicine, University of Saskatchewan, 52 Campus Drive, Saskatoon, SK S7N 5B4 Canada.
authors.forename: Shankaramurthy
authors.initials: S
authors.lastname: Channabasappa
authors.affiliation: Department of Veterinary Biomedical Sciences, Western College of Veterinary Medicine, University of Saskatchewan, 52 Campus Drive, Saskatoon, SK S7N 5B4 Canada.
authors.forename: Baljit
authors.initials: B
authors.lastname: Singh
keywords: BAL; Barn dust; CpG DNA; Macrophages; Neutrophils; TLR9