Pyroptosis is a pro-inflammatory form of programmed cell death executed by gasdermin family proteins. Which caspase is responsible for canonical inflammasome-activated pyroptosis in macrophages infected with intracellular bacteria?

• A Caspase-8, activated downstream of death receptor TRAIL-R2
• B Caspase-4/5 (human) activated by cytosolic LPS sensing directly
• C Caspase-9, activated by cytochrome c release and apoptosome formation
• D Caspase-1, activated by NLRP3 or NLRC4 inflammasome assembly ✓

Explanation

Canonical inflammasome-mediated pyroptosis is executed by caspase-1, which is activated when NLRP3 (danger signals, crystals, ATP), NLRC4 (flagellin, T3SS rod protein), or AIM2 (cytosolic DNA) inflammasomes assemble and recruit ASC and pro-caspase-1. Active caspase-1 cleaves gasdermin D at D275, releasing the pore-forming N-terminal fragment that inserts into the plasma membrane, causing cell swelling and lytic death with IL-1β and IL-18 release. Non-canonical pyroptosis (caspase-4/5 in humans, caspase-11 in mice) responds to direct cytosolic LPS binding, also cleaving gasdermin D.

Reference: Robbins & Cotran Pathologic Basis of Disease, 10th ed.

High-yield for: NEET PGINI-CETNExTFMGEUSMLEPLABMRCP

Written and medically reviewed by the StethoPrep medical team.