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Updated: Feb 9, 2026

Activation and Measurement of NLRP3 Inflammasome Activity Using IL-1β in Human Monocyte-derived Dendritic Cells
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Activation and Measurement of NLRP3 Inflammasome Activity Using IL-1β in Human Monocyte-derived Dendritic Cells

Published on: May 22, 2014

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The mitochondrial protease HtrA2 restricts the NLRP3 and AIM2 inflammasomes

Ian Gaël Rodrigue-Gervais1,2, Karine Doiron3, Claudia Champagne3

  • 1Department of Medicine, McGill University, Montréal, Québec, H3G 0B1, Canada. ian.rodrigue-gervais@iaf.inrs.ca.

Scientific Reports
|June 2, 2018
PubMed

Insights

The mitochondrial protease HtrA2 (high-temperature requirement A2) limits inflammasome activation by controlling ASC levels. Loss of HtrA2 protease activity enhances inflammasome responses, highlighting its role in host defense.

Area of Science:

  • Immunology
  • Cell Biology
  • Mitochondrial Biology

Background:

  • The inflammasome pathway is essential for intracellular host defense against pathogens.
  • Mitochondria are critical regulators of inflammasome activation, but the precise mechanisms remain unclear.
  • Mitochondrial homeostasis is linked to the control of inflammasome signaling.

Purpose of the Study:

  • To investigate the role of the mitochondrial serine protease HtrA2 in regulating inflammasome activation.
  • To elucidate the mechanisms by which HtrA2 influences inflammasome signaling pathways.
  • To determine if HtrA2 protease activity is essential for controlling inflammasome responses.

Main Methods:

  • Assessed inflammasome activation in macrophages ex vivo and in vivo.
  • Utilized genetic disruption of HtrA2 protease activity.
  • Investigated the impact of HtrA2 on autophagy and inflammasome adaptor ASC accumulation.

Main Results:

  • HtrA2 protease activity restricts ASC-dependent NLRP3 and AIM2 inflammasome activation.
  • Disruption of HtrA2 protease activity leads to heightened inflammasome responses.
  • HtrA2 regulates autophagy and prevents excessive ASC accumulation, thereby controlling inflammasome signaling duration and magnitude.

Conclusions:

  • HtrA2 acts as a critical mitochondrial quality control effector that restrains NLRP3 and AIM2 inflammasome activation.
  • HtrA2 protease activity is crucial for maintaining immune homeostasis by attenuating inflammasome responses.
  • These findings identify a novel link between mitochondrial function and inflammasome regulation.

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