Cell Reports (Jul 2016)

A Fluorescent Reporter Mouse for Inflammasome Assembly Demonstrates an Important Role for Cell-Bound and Free ASC Specks during In Vivo Infection

  • Te-Chen Tzeng,
  • Stefan Schattgen,
  • Brian Monks,
  • Donghai Wang,
  • Anna Cerny,
  • Eicke Latz,
  • Katherine Fitzgerald,
  • Douglas T. Golenbock

DOI
https://doi.org/10.1016/j.celrep.2016.06.011
Journal volume & issue
Vol. 16, no. 2
pp. 571 – 582

Abstract

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Inflammasome activation is associated with numerous diseases. However, in vivo detection of the activated inflammasome complex has been limited by a dearth of tools. We have developed transgenic mice that ectopically express the fluorescent adaptor protein, apoptosis-associated speck-like protein containing a caspase recruitment domain (ASC) and characterized the formation of assembled inflammasome complexes (“specks”) in primary cells and tissues. In addition to hematopoietic cells, we have found that a stromal population in the lung tissues formed specks during the early phase of influenza infection, whereas myeloid cells showed speck formation after 2 days. In a peritonitis and group B streptococcus infection model, a higher percentage of neutrophils formed specks at early phases of infection, while dendritic cells formed specks at later time points. Furthermore, speck-forming cells underwent pyroptosis and extensive release of specks to the extracellular milieu in vivo. These data underscore the importance of free specks during inflammatory processes in vivo.