New Developments in the Understanding of Immunology in Silicosis
New Developments in the Understanding of Immunology in Silicosis
Purpose of review: There is compelling evidence that the immune responses induced by crystalline silica particles are implicated in the development of silicosis. This article reviews recent observations which further delineate how innate and adaptive immunity are involved in this lung disease.
Recent findings: First, silica particles are recognized to have pathogen-associated molecular patterns by the innate immune system. The MARCO receptor expressed on the surface of macrophages appears crucial for the recognition and the uptake of silica as well as the activation of these immune cells in silicosis. Additional data support a major role of inflammation (mast cells, B lymphocytes and TNFα) in the development of lung fibrosis but also cancer. Silica-induced acute inflammation is accompanied by thrombosis; strongly suggesting that inhaled silica particles may also induce extrapulmonary lesions. Surprisingly, a pronounced anti-inflammatory reaction may also contribute to silica-induced lung fibrosis in mice and represent an additional etiopathogenic pathway of silicosis. Interestingly, it has been proposed that the pulmonary expression of IL-9 (a T lymphocyte-related interleukin) or Heme oxygenase-1 (an anti-inflammatory molecule) attenuated silicotic disease progression in animals.
Summary: New pathogenic routes involving innate receptors and antiinflammation as well as new antifibrotic immune mediators have been recently described in experimental silicosis, highlighting new potential therapeutic targets and strategies.
Contrary to common opinion, interstitial pulmonary fibrosis resulting from workplace exposure to crystalline silica particles (silicosis) is not a disease of the past, in particular in developing countries the situation appears very prevalent. Several lines of evidence support the view that the pathogenesis of silicosis involves uncontrolled immune processes. Indeed, the fundamental concept, usually put forward to explain the pathogenesis of this disease, is relatively simple: a chronic inflammatory status (referred to as alveolitis) in which the immune cells are activated and release toxic mediators, damages the pulmonary architecture, modulates the accumulation of mesenchymal cells and their connective tissue products, and may transform normal lung cells to tumor cells (see Figure 1).
(Enlarge Image)
Major biological processes associated with injury and fibrosis of the lower respiratory tract in silicosis.
Purpose of review: There is compelling evidence that the immune responses induced by crystalline silica particles are implicated in the development of silicosis. This article reviews recent observations which further delineate how innate and adaptive immunity are involved in this lung disease.
Recent findings: First, silica particles are recognized to have pathogen-associated molecular patterns by the innate immune system. The MARCO receptor expressed on the surface of macrophages appears crucial for the recognition and the uptake of silica as well as the activation of these immune cells in silicosis. Additional data support a major role of inflammation (mast cells, B lymphocytes and TNFα) in the development of lung fibrosis but also cancer. Silica-induced acute inflammation is accompanied by thrombosis; strongly suggesting that inhaled silica particles may also induce extrapulmonary lesions. Surprisingly, a pronounced anti-inflammatory reaction may also contribute to silica-induced lung fibrosis in mice and represent an additional etiopathogenic pathway of silicosis. Interestingly, it has been proposed that the pulmonary expression of IL-9 (a T lymphocyte-related interleukin) or Heme oxygenase-1 (an anti-inflammatory molecule) attenuated silicotic disease progression in animals.
Summary: New pathogenic routes involving innate receptors and antiinflammation as well as new antifibrotic immune mediators have been recently described in experimental silicosis, highlighting new potential therapeutic targets and strategies.
Contrary to common opinion, interstitial pulmonary fibrosis resulting from workplace exposure to crystalline silica particles (silicosis) is not a disease of the past, in particular in developing countries the situation appears very prevalent. Several lines of evidence support the view that the pathogenesis of silicosis involves uncontrolled immune processes. Indeed, the fundamental concept, usually put forward to explain the pathogenesis of this disease, is relatively simple: a chronic inflammatory status (referred to as alveolitis) in which the immune cells are activated and release toxic mediators, damages the pulmonary architecture, modulates the accumulation of mesenchymal cells and their connective tissue products, and may transform normal lung cells to tumor cells (see Figure 1).
(Enlarge Image)
Major biological processes associated with injury and fibrosis of the lower respiratory tract in silicosis.
