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Activation and Measurement of NLRP3 Inflammasome Activity Using IL-1β in Human Monocyte-derived Dendritic Cells
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Influenza virus activates inflammasomes via its intracellular M2 ion channel

Takeshi Ichinohe1, Iris K Pang, Akiko Iwasaki

  • 1Department of Immunobiology, Yale University School of Medicine, New Haven, Connecticut, USA.

Nature Immunology
|April 13, 2010
PubMed

Insights

The influenza virus M2 protein activates the NLRP3 inflammasome pathway. This discovery reveals a new mechanism for how influenza infection triggers immune responses by sensing changes in cellular ion concentrations.

Area of Science:

  • Virology
  • Immunology
  • Molecular Biology

Background:

  • Influenza virus is a significant human and animal pathogen.
  • The Nod-like receptor NLRP3 (NLR family, pyrin domain containing 3) inflammasome is activated by various pathogens, including influenza virus.
  • The precise mechanism of influenza virus-induced NLRP3 inflammasome activation remains unclear.

Purpose of the Study:

  • To elucidate the mechanism by which influenza virus activates the NLRP3 inflammasome.
  • To identify the viral component responsible for inflammasome activation.
  • To characterize the cellular processes involved in this activation pathway.

Main Methods:

  • Investigated the role of the influenza virus M2 protein in inflammasome activation.
  • Utilized primed macrophages and dendritic cells to assess M2 channel activity.
  • Examined the requirement for M2 protein localization to the Golgi apparatus and pH gradient dependence.

Main Results:

  • The influenza virus M2 protein directly stimulates the NLRP3 inflammasome pathway.
  • M2 channel activity is essential for influenza-induced inflammasome activation.
  • M2 protein's ion channel function is sufficient to activate inflammasomes in immune cells.
  • Activation is dependent on M2's Golgi localization and the resulting pH gradient.

Conclusions:

  • The influenza virus M2 protein acts as a direct activator of the NLRP3 inflammasome.
  • Influenza virus infection activates inflammasomes via M2 protein-mediated disruption of intracellular ion homeostasis.
  • This study identifies sensing of ionic concentration disturbances as a novel pathogen recognition pathway.

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