TLR4-MyD88 signaling pathway is responsible for acute lung inflammation induced by reclaimed water

Abstract

Previous research found that inhalation exposure of reclaimed water could cause severe pulmonary inflammation, and the endotoxin was proposed to be the key risk factor. To further support this view, the toxic effects of different reclaimed water induced by acute inhalation exposure were compared between wildtype C57BL/6J and TLR4 signaling pathway defect mice. It was found that reclaimed water with high levels of endotoxin could induce strong inflammation in wildtype mice, but not in Tlr4^-/- and MyD88^-/- mutants. The mixed bacterial culture from the reclaimed water showed very weak response in wildtype mice and no response in TLR4-signaling pathway deficient mice, which further suggested that the cell-bound endotoxins contribute little in the inflammation induced by reclaimed water. In addition, conditional knockout of the Tlr4 gene in myeloid cells resulted in a significant reduction of sensitivity to the reclaimed water in mutants, which indicates that myeloid cells play the most important role in the defensive immune system against the pollutants in the water. In general, this study demonstrated that the TLR4-MyD88 signaling pathway is responsible for the acute lung inflammation induced by reclaimed water, which excludes the possibility of other signaling pathway dependent inflammation inducers in reclaimed water.

Keywords: Endotoxin; Inhalation exposure; MyD88; Reclaimed water; TLR4.