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Updated: Jun 7, 2026

Activation and Measurement of NLRP3 Inflammasome Activity Using IL-1β in Human Monocyte-derived Dendritic Cells
Published on: May 22, 2014
Activation of the NLRP3 inflammasome by intracellular poly I:C
Jayant V Rajan1, Sarah E Warren, Edward A Miao
1Institute for Systems Biology, Seattle, WA 98103, USA.
Abstract:
Several RNA viruses can be detected by the inflammasome, which promotes IL-1β and IL-18 secretion, but the underlying mechanisms of detection remain unclear. Cytosolic dsRNA is a replication intermediate of many RNA viruses. We show here that transfection of the dsRNA analogue poly I:C activates the NLRP3 inflammasome via a pathway requiring endosomal acidification. This detection is independent of the other poly I:C sensors: TLR3 and MDA5. These results suggest a mechanism by which cytosolic dsRNA produced during viral infection could activate the NLRP3 inflammasome.
Insights
The inflammasome detects RNA viruses by sensing double-stranded RNA (dsRNA) through endosomal acidification, independent of TLR3 and MDA5 sensors. This finding clarifies how viral dsRNA activates the NLRP3 inflammasome, promoting immune responses.
Area of Science:
- Immunology
- Virology
- Molecular Biology
Background:
- The inflammasome is crucial for detecting RNA viruses and secreting IL-1β and IL-18.
- The precise mechanisms by which RNA viruses are detected by the inflammasome are not fully understood.
- Cytosolic double-stranded RNA (dsRNA) is a key intermediate in the replication of many RNA viruses.
Purpose of the Study:
- To investigate the mechanism by which cytosolic dsRNA activates the inflammasome.
- To determine if the NLRP3 inflammasome is involved in dsRNA detection.
- To elucidate the role of endosomal acidification in dsRNA-mediated inflammasome activation.
Main Methods:
- Transfection of cells with the dsRNA analogue poly I:C.
- Assessment of inflammasome activation, specifically NLRP3.
- Investigation of the requirement for endosomal acidification in the activation pathway.
- Evaluation of the independence of this pathway from TLR3 and MDA5 sensors.
Main Results:
- Poly I:C transfection activates the NLRP3 inflammasome.
- This activation is dependent on endosomal acidification.
- The dsRNA-mediated NLRP3 inflammasome activation is independent of TLR3 and MDA5.
- A novel pathway for dsRNA detection by the NLRP3 inflammasome was identified.
Conclusions:
- Cytosolic dsRNA, a viral replication intermediate, can activate the NLRP3 inflammasome.
- Endosomal acidification is a critical step in this dsRNA detection pathway.
- This mechanism provides insight into how viral infections trigger inflammasome-mediated immune responses.
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