A Fluorescent Reporter Mouse for Inflammasome Assembly Demonstrates an Important Role for Cell-Bound and Free ASC Specks during In Vivo Infection
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 co...
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| Format: | Article |
| Language: | English |
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Elsevier
2016-07-01
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| Series: | Cell Reports |
| Online Access: | http://www.sciencedirect.com/science/article/pii/S2211124716307306 |
| _version_ | 1828824801489190912 |
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| author | Te-Chen Tzeng Stefan Schattgen Brian Monks Donghai Wang Anna Cerny Eicke Latz Katherine Fitzgerald Douglas T. Golenbock |
| author_facet | Te-Chen Tzeng Stefan Schattgen Brian Monks Donghai Wang Anna Cerny Eicke Latz Katherine Fitzgerald Douglas T. Golenbock |
| author_sort | Te-Chen Tzeng |
| collection | DOAJ |
| description | 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. |
| first_indexed | 2024-12-12T14:05:12Z |
| format | Article |
| id | doaj.art-8765119fb6d44bc29bdd3ccb294d1e16 |
| institution | Directory Open Access Journal |
| issn | 2211-1247 |
| language | English |
| last_indexed | 2024-12-12T14:05:12Z |
| publishDate | 2016-07-01 |
| publisher | Elsevier |
| record_format | Article |
| series | Cell Reports |
| spelling | doaj.art-8765119fb6d44bc29bdd3ccb294d1e162022-12-22T00:22:15ZengElsevierCell Reports2211-12472016-07-0116257158210.1016/j.celrep.2016.06.011A Fluorescent Reporter Mouse for Inflammasome Assembly Demonstrates an Important Role for Cell-Bound and Free ASC Specks during In Vivo InfectionTe-Chen Tzeng0Stefan Schattgen1Brian Monks2Donghai Wang3Anna Cerny4Eicke Latz5Katherine Fitzgerald6Douglas T. Golenbock7Division of Infectious Diseases and Immunology, University of Massachusetts Medical School, Worcester, MA 01605, USADivision of Infectious Diseases and Immunology, University of Massachusetts Medical School, Worcester, MA 01605, USADivision of Infectious Diseases and Immunology, University of Massachusetts Medical School, Worcester, MA 01605, USADivision of Infectious Diseases and Immunology, University of Massachusetts Medical School, Worcester, MA 01605, USADivision of Infectious Diseases and Immunology, University of Massachusetts Medical School, Worcester, MA 01605, USADivision of Infectious Diseases and Immunology, University of Massachusetts Medical School, Worcester, MA 01605, USADivision of Infectious Diseases and Immunology, University of Massachusetts Medical School, Worcester, MA 01605, USADivision of Infectious Diseases and Immunology, University of Massachusetts Medical School, Worcester, MA 01605, USAInflammasome 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.http://www.sciencedirect.com/science/article/pii/S2211124716307306 |
| spellingShingle | Te-Chen Tzeng Stefan Schattgen Brian Monks Donghai Wang Anna Cerny Eicke Latz Katherine Fitzgerald Douglas T. Golenbock A Fluorescent Reporter Mouse for Inflammasome Assembly Demonstrates an Important Role for Cell-Bound and Free ASC Specks during In Vivo Infection Cell Reports |
| title | A Fluorescent Reporter Mouse for Inflammasome Assembly Demonstrates an Important Role for Cell-Bound and Free ASC Specks during In Vivo Infection |
| title_full | A Fluorescent Reporter Mouse for Inflammasome Assembly Demonstrates an Important Role for Cell-Bound and Free ASC Specks during In Vivo Infection |
| title_fullStr | A Fluorescent Reporter Mouse for Inflammasome Assembly Demonstrates an Important Role for Cell-Bound and Free ASC Specks during In Vivo Infection |
| title_full_unstemmed | A Fluorescent Reporter Mouse for Inflammasome Assembly Demonstrates an Important Role for Cell-Bound and Free ASC Specks during In Vivo Infection |
| title_short | A Fluorescent Reporter Mouse for Inflammasome Assembly Demonstrates an Important Role for Cell-Bound and Free ASC Specks during In Vivo Infection |
| title_sort | fluorescent reporter mouse for inflammasome assembly demonstrates an important role for cell bound and free asc specks during in vivo infection |
| url | http://www.sciencedirect.com/science/article/pii/S2211124716307306 |
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