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.
Louvain Centre for Toxicology and Applied Pharmacology, Université catholique de Louvain, 1200 Brussels, Belgium.
Giulia
G
Giordano
Sybille
S
van den Brûle
Sandra
S
Lo Re
Perrine
P
Triqueneaux
Francine
F
Uwambayinema
Yousof
Y
Yakoub
Isabelle
I
Couillin
Bernhard
B
Ryffel
Thomas
T
Michiels
Jean-Christophe
JC
Renauld
Dominique
D
Lison
François
F
Huaux
D000818:Animals; D002908:Chronic Disease; D003713:Dendritic Cells / Q000502:physiology; D004195:Disease Models, Animal; D007249:Inflammation / Q000209:etiology*; D007370:Interferon Type I / Q000502:physiology*; D008264:Macrophages / Q000502:physiology; D051379:Mice; D008810:Mice, Inbred C57BL; D015398:Signal Transduction; D012829:Silicosis / Q000276:immunology*
D007370:Interferon Type I