A Fluorescent Reporter Mouse for Inflammasome Assembly Demonstrates an Important Role for Cell-Bound and Free ASC Specks during In Vivo Infection
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Schattgen, Stefan A.
Monks, Brian G.
Cerny, Anna M.
Fitzgerald, Katherine A.
Golenbock, Douglas T.
UMass Chan AffiliationsDepartment of Medicine, Division of Infectious Diseases and Immunology
Document TypeJournal Article
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AbstractInflammasome 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.
SourceCell Rep. 2016 Jul 12;16(2):571-82. doi: 10.1016/j.celrep.2016.06.011. Epub 2016 Jun 23. Link to article on publisher's site
Permanent Link to this Itemhttp://hdl.handle.net/20.500.14038/39982
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This is an open access article under the CC BY license (http://creativecommons.org/licenses/by/4.0/).
Except where otherwise noted, this item's license is described as <p>This is an open access article under the CC BY license (http://creativecommons.org/licenses/by/4.0/).</p>