EspF acts as a molecular scaffold to facilitate TRIM25-mediated NLRP3 inflammasome activation during mycobacterial infection

The mycobacterial ESX-1 effector EspF is a conserved activator of the NLRP3 inflammasome in Mycobacterium tuberculosis, M. bovis and M. marinum. EspF augments IL-1β and IL-18 release, ASC speck formation, caspase-1 activation and GSDMD-mediated pyroptosis in THP-1 cells, and acts as a scaffold bridging TRIM25 to NLRP3, promoting K63-linked ubiquitination of NLRP3. Mice infected with M. bovis BCG overexpressing EspF showed worse lung lesions and higher bacterial burdens.