[HTML][HTML] A fluorescent reporter mouse for inflammasome assembly demonstrates an important role for cell-bound and free ASC specks during in vivo infection

TC Tzeng, S Schattgen, B Monks, D Wang, A Cerny… - Cell reports, 2016 - cell.com
TC Tzeng, S Schattgen, B Monks, D Wang, A Cerny, E Latz, K Fitzgerald, DT Golenbock
Cell reports, 2016cell.com
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 …
Summary
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.
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