Type A cholesterol-dependent cytolysins translocate to the trans-Golgi network for NLRP3 inflammasome activation.

ABSTRACT: Cholesterol-dependent cytolysins (CDCs) constitute the largest group of pore-forming toxins and serve as critical virulence factors for diverse pathogenic bacteria. Several CDCs are known to activate the NLRP3 inflammasome, although the mechanisms are unclear. Here we discovered that multiple CDCs, which we referred to as type A CDCs, were internalized and translocated to the trans-Golgi network (TGN) to remodel it into a platform for NLRP3 activation through a unique peeling membrane mechanism. Potassium efflux was dispensable for CDC-mediated TGN remodeling and NLRP3 recruitment, but was required for the recruitment of the downstream adaptor ASC. In contrast, desulfolysin, which we referred to as type B CDC, was not internalized or translocated to the TGN due to its distinct C-terminal d

SUBMITTER: Xiao N 

PROVIDER: S-EPMC12443345 | biostudies-literature | 2025 Sep

REPOSITORIES: biostudies-literature