Figure 7.

Schematic of the relationship between the NLRP3 inflammasome and speck. NLRP3–ASC specks form by rapid relocation of these proteins into a perinuclear toroidal structure. Specks allow inflammasome complexes to be activated at a lower stimulus threshold and thus facilitate an optimal inflammasome response to weaker signals. However, inflammasome complexes also form independently of the speck and stronger signals may not require or elicit speck formation. The speck likely sheds small inflammasome complexes where caspase-1 becomes active. As caspase-1 activity regulates the size of the speck, active caspase-1 may facilitate the release of small inflammasome complexes, acting as an intracellular feedforward loop maximizing IL-1β processing.