Type I interferon signaling contributes to chronic inflammation in a murine model of silicosis.

Lung disorders induced by inhaled inorganic particles such as crystalline silica are characterized by chronic inflammation and pulmonary fibrosis. Here, we demonstrate the importance of type I interferon (IFN) in the development of crystalline silica-induced lung inflammation in mice, revealing that viruses and inorganic particles share similar signaling pathways. We found that instillation of silica is followed by the upregulation of IFN-beta and IRF-7 and that granulocytes (GR1(+)) and macrophages/dendritic cells (CD11c(+)) are major producers of type I IFN in response to silica. Two months after silica administration, both IFNAR- and IRF-7-deficient mice produced significantly less pulmonary inflammation and chemokines (KC and CCL2) than competent mice but developed similar lung fibrosis. Our data indicate that type I IFN contributes to the chronic lung inflammation that accompanies silica exposure in mice. Type I IFN is, however, dispensable in the development of silica-induced acute lung inflammation and pulmonary fibrosis.