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

EspF acts as a molecular scaffold to enhance TRIM25-mediated NLRP3 inflammasome activation during mycobacterial infection, promoting hyperinflammation and bacterial survival.

• Why it matters: Understanding how mycobacteria manipulate host immune responses is crucial for developing better treatments, as the specific bacterial effectors involved in inflammasome activation are largely unknown.
• What they did: The study systematically screened ESX-1 effectors and identified EspF as a conserved activator across pathogenic mycobacteria, demonstrating its interaction with NLRP3 and TRIM25 through proteomic and cellular assays.
• The result: Overexpression of EspF increased inflammasome activation, pyroptosis, and bacterial burden in vivo, revealing the EspF-TRIM25-NLRP3 axis as a key driver of hyperinflammation and mycobacterial pathogenesis.