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Updated: Jan 20, 2026

Evaluation of Caspase Activation to Assess Innate Immune Cell Death
Published on: January 20, 2023
Inflammasomes: Threat-Assessment Organelles of the Innate Immune System
Charles L Evavold1, Jonathan C Kagan1
1Division of Gastroenterology, Boston Children's Hospital, Harvard Medical School, Boston, MA 02115, USA; Program in Immunology, Harvard Medical School, Boston, MA 02115, USA.
Abstract:
Inflammasomes are supramolecular organizing centers that operate to drive interleukin-1 (IL-1)-dependent inflammation. Depending on context, inflammatory caspases act upstream or downstream of inflammasome assembly, serving as the principal enzymes that control activities of these organelles. In this review, we discuss mechanisms of inflammasome assembly and signaling. We posit that upstream regulatory proteins, classically known as pattern-recognition receptors, operate to assess infectious and non-infectious threats to the host. Threat assessment is achieved through two general strategies: (1) direct binding of receptors to microbial or host-derived ligands or (2) indirect detection of changes in cellular homeostasis. Upon activation, these upstream regulatory factors seed the assembly of inflammasomes, leading to IL-1 family cytokine release from living (hyperactive) or dead (pyroptotic) cells. The molecular and physiological consequences of these distinct cell fate decisions are discussed.
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