The complex cascade of cellular events governing inflammasome activation and IL-1β processing in response to inhaled particles

The innate immune system is the first line of defense against inhaled particles. Macrophages serve important roles in particle clearance and inflammatory reactions. Following recognition and internalization by phagocytes, particles are taken up in vesicular phagolysosomes. Intracellular phagosomal leakage, redox unbalance and ionic movements induced by toxic particles result in pro-IL-1 beta expression, inflammasome complex engagement, caspase-1 activation, pro-IL-1 beta cleavage, biologically-active IL-1 beta release and finally inflammatory cell death termed pyroptosis. In this review, we summarize the emerging signals and pathways involved in the expression, maturation and secretion of IL-1 beta during these responses to particles. We also highlight physicochemical characteristics of particles (size, surface and shape) which determine their capacity to induce inflammasome activation and IL-1 beta processing.