title: A Fluorescent Reporter Mouse for Inflammasome Assembly Demonstrates an Important Role for Cell-Bound and Free ASC Specks during In Vivo Infection.
abstract: 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.
authors.affiliation: Division of Infectious Diseases and Immunology, University of Massachusetts Medical School, Worcester, MA 01605, USA.
authors.forename: Te-Chen
authors.initials: TC
authors.lastname: Tzeng
authors.affiliation: Division of Infectious Diseases and Immunology, University of Massachusetts Medical School, Worcester, MA 01605, USA.
authors.forename: Stefan
authors.initials: S
authors.lastname: Schattgen
authors.affiliation: Division of Infectious Diseases and Immunology, University of Massachusetts Medical School, Worcester, MA 01605, USA; Institute of Innate Immunity, University of Bonn, Sigmund-Freud-Strasse 25, 53127 Bonn, Germany.
authors.forename: Brian
authors.initials: B
authors.lastname: Monks
authors.affiliation: Division of Infectious Diseases and Immunology, University of Massachusetts Medical School, Worcester, MA 01605, USA.
authors.forename: Donghai
authors.initials: D
authors.lastname: Wang
authors.affiliation: Division of Infectious Diseases and Immunology, University of Massachusetts Medical School, Worcester, MA 01605, USA.
authors.forename: Anna
authors.initials: A
authors.lastname: Cerny
authors.affiliation: Division of Infectious Diseases and Immunology, University of Massachusetts Medical School, Worcester, MA 01605, USA; Institute of Innate Immunity, University of Bonn, Sigmund-Freud-Strasse 25, 53127 Bonn, Germany.
authors.forename: Eicke
authors.initials: E
authors.lastname: Latz
authors.affiliation: Division of Infectious Diseases and Immunology, University of Massachusetts Medical School, Worcester, MA 01605, USA.
authors.forename: Katherine
authors.initials: K
authors.lastname: Fitzgerald
authors.affiliation: Division of Infectious Diseases and Immunology, University of Massachusetts Medical School, Worcester, MA 01605, USA. Electronic address: douglas.golenbock@umassmed.edu.
authors.forename: Douglas T
authors.initials: DT
authors.lastname: Golenbock
mesh_terms: D000818:Animals; D053468:CARD Signaling Adaptor Proteins / Q000096:biosynthesis / Q000235:genetics*; D005260:Female; D015870:Gene Expression; D017930:Genes, Reporter; D058847:Inflammasomes / Q000378:metabolism*; D008297:Male; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D009976:Orthomyxoviridae Infections / Q000276:immunology / Q000378:metabolism; D010538:Peritonitis / Q000276:immunology / Q000378:metabolism; D055503:Protein Multimerization; D013290:Streptococcal Infections / Q000276:immunology / Q000378:metabolism
chemical_list: D053468:CARD Signaling Adaptor Proteins; D058847:Inflammasomes; C498534:Pycard protein, mouse