Huaux, François
[UCL]
Inhalation of toxic inorganic particles such as crystalline form of silica is associated with a variety of pulmonary diseases, including alveolitis, fibrosis and lung cancer. The lung response induced by crystalline silica particles involves a massive recruitment of inflammatory cells, such as macrophages and neutrophils, apoptosis of pulmonary cells, the production of pro-inflammatory mediators, such as cytokines and eicosanoids, and the release of growth factors for fibroblasts that collectively are believed to lead to the development of fibrosing nodules and impairment of pulmonary function. While the role of the adaptive immune system, particularly the functions of T helper lymphocytes, has already been investigated in particle-induced lung diseases, little is known about the importance of the innate immune system. Some evidence suggests that innate immune receptors expressed by macrophages are involved in the recognition, uptake and possibly toxicity of silica, probably in relation with the surface characteristics of these particles. With our experimental approach, we demonstrate the important role of type I interferon in the development of this inflammatory reaction, highlighting that viral and inorganic particles share a similar signaling pathway. We also show that the inflammatory response induced by silica is dependent on the inflammasome. Stimulation of macrophages with silica results in the activation of inflammasome pathway and inflammasome-deficient mice failed to produce the proinflammatory cytokines interleukin (IL)-1beta and IL-18 and developed reduced lung inflammation in response to silica. These new observations highlight the key role for the viral pathway and the inflammasome in the pathogenesis of particles induced-lung diseases and suggest that the innate immunity of the lung may represent a new target for controlling inorganic particle toxicity.
Bibliographic reference |
Huaux, François. TLR pathways implication in silicosis..TLR receptors from research to medical applications, Inserm Workshop (Saint Raphael, France, du 16/10/2008 au 18/10/2008). |
Permanent URL |
http://hdl.handle.net/2078.1/181755 |