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EFFECTS OF DIESEL EXHAUST ON TLR3 EXPRESSION IN MICE
Citation:
CIENCEWICKI, J., K. GOWDY, IAN I. GILMOUR, AND I. JASPERS. EFFECTS OF DIESEL EXHAUST ON TLR3 EXPRESSION IN MICE. Presented at Society of Toxicology Annual Meeting, San Diego, CA, March 05 - 09, 2006.
Description:
There are a variety of intrinsic as well as extrinsic factors, such as exposure to air pollution that can affect the pathogenesis of respiratory infections. Exposure to diesel exhaust (DE) emissions can alter host defense and immune responses and we have previously demonstrated that DE enhances the susceptibility to influenza infections and influenza-induced expression of toll-like receptor 3 (TLR3) in human respiratory epithelial cells in vitro. The purpose of this study was to confirm and expand these observations in vivo. BALB/c mice were exposed to air, 0.5 or 2 mg/m3 of DE for 4 hours/day for 5 days. One hour after the final exposure, mice were intratracheally instilled with influenza A/Bangkok/1/79 virus or vehicle and the animals were sacrificed 18 hours post-infection. Exposure to 0.5 mg/m3 DE enhanced viral titers, as indicated by increased levels of influenza hemagglutinin (HA) mRNA levels, a marker of viral titers. Similarly, exposure to 0.5mg/m3 DE also enhanced influenza-induced TLR3 as well as TLR7 expression in mouse lung. Additionally, the two major branches of TLR3¿s downstream signaling cascade were also enhanced at this exposure level. Increased signaling in both the inflammatory and interferon branches of the TLR3 pathway was indicated by increased expression of IL-6 and IFN-¿, respectively. In contrast, while exposure to DE enhanced influenza-induced TLR3 expression in the lung, exposure to DE had no effect on influenza-induced TLR3 and TLR7 expression in lymph nodes. Taken together these results indicate that exposure to DE could potentially alter the susceptibility and response to viral infections by increasing the expression and signaling of TLR3 in the lung.