Fig. 6: Proposed model for the role of cathepsin on NAIP/NLRC4-mediated IL-1β secretion.
From: Lysosomal cathepsins act in concert with Gasdermin-D during NAIP/NLRC4-dependent IL-1β secretion
Flagellin stimulation leads to lysosome Membrane Permeabilization (LMP) resulting in the leakage of cathepsins into cell cytosol [27] where they participate in the regulation of NAIP/NLRC4-mediated responses. In contrast to that described for NLRP3 agonists [28,29,30,31, 34, 36,37,38], cathepsins did not interfere with the induction of pro-IL-1β, ASC speck formation or caspase-1 activity in response to flagellin, demonstrating their role downstream to NAIP/NLRC4 assembly. Here we propose the cooperation between cathepsins and GSDMD for the optimal IL-1β secretion by a mechanism that could involve mature IL-1β transportation to the plasma membrane [45] (1) or its release by extracellular vesicles [46,47,48,49,50] (2).
