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Macrophage Swelling Turns On Antiviral Signals and Drives Stronger Inflammation

Peer-reviewed data point to cell-volume control as a switch for macrophage interferon responses.

Overview

  • Researchers at the University of Manchester reported Thursday in the Journal of Cell Biology that disturbing macrophage volume control switches on type I interferon signals.
  • Deleting the Volume‑Regulated Anion Channel, an ion channel that helps cells restore size, left macrophages swollen under mild low‑osmotic conditions.
  • The swelling rewired gene activity toward antiviral and nucleic acid‑sensing pathways through a DNA‑ and TBK1‑dependent route that did not use the cGAS sensor.
  • In cell experiments, VRAC‑deficient macrophages mounted a stronger defense against Influenza A virus than wild‑type cells.
  • In mouse hyperinflammation models, VRAC‑deficient mice produced higher levels of a key inflammatory mediator, and the authors said VRAC may be a drug target that requires more testing.