Fig. 6

Fig. 6. Proposed working models showing the induction of Gsdme-mediated pyroptotic cell death in macrophages and neutrophils during chronic inflammation. During chronic inflammation, inflammatory signals from the inflamed tissue reach hematopoietic tissue and promote the differentiation of HSPCs to macrophages and neutrophils (emergency myelopoiesis). A) Neutrophils are recruited by a gradient of inflammatory signals to the inflamed tissue and once there they develop their function and die by pyroptosis allowing the regulation of the number of neutrophils needed to resolve the inflammation. B) Inhibition of the neutrophil inflammasome by forced expression of DN-Asc impaired pyroptosis and leads to accumulation of neutrophils in the inflamed tissue. C) Activation of the neutrophil inflammasome by forced expression of Gbp4 further promotes pyroptosis of neutrophils infiltrated in the inflamed skin, resulting in neutrophil clearance. A similar mechanism operates in macrophages (not shown).