The involvement of the innate immune system in the lung toxicity induced by crystalline silica particles in mice
(2009)
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- (en) Inhaled particles such as crystalline silica (CSP) may induce the development of chronic lung inflammation (alveolitis), fibrosis and cancer. Inflammatory cells that accumulate in the lung in response to CSP are, in part, responsible for the release of growth factors and cytokines (e.g. IL-1β, TNFα, PDGF and TGF-β) that amplify alveolitis and activate fibroblasts. Here we addressed early aspects of silicosis and focused on the role played by inflammatory mediators in the initial steps of CSP-induced toxicity in mice. The study reveals that CSP induce a type I interferon signature (IFN-β, IRF-7, OAS) qualitatively similar to viral infection in the lung of mice. The use of mice deficient for type I interferon receptor (IFNAR) showed that this response contributes to maintain the pulmonary inflammation induced by CSP. An implication of pulmonary neutrophils in this mechanism is suggested, underlining a potentially new function for these cells. The thesis also shows that the IL-1 pathway (MyD88, ASC, IL-1R1) plays a role in the development and maintenance of the pulmonary inflammation induced by CSP. Blockade of the IL-1 pathway did, however, not prevent the development of silicotic nodules and moreover induced alveolar proteinosis and diffuse fibrosis in mice deficient for MyD88 or IL- 1R1, similar to acute silicosis in humans. These results indicate that blocking the IL-1 pathway is probably not a useful therapeutic approach in silicosis.
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Giordano, G. (2009). The involvement of the innate immune system in the lung toxicity induced by crystalline silica particles in mice. https://hdl.handle.net/2078.5/131415