| First Author | Talley S | Year | 2019 |
| Journal | J Immunol | Volume | 203 |
| Issue | 9 | Pages | 2497-2507 |
| PubMed ID | 31562211 | Mgi Jnum | J:280943 |
| Mgi Id | MGI:6370322 | Doi | 10.4049/jimmunol.1900619 |
| Citation | Talley S, et al. (2019) A Caspase-1 Biosensor to Monitor the Progression of Inflammation In Vivo. J Immunol 203(9):2497-2507 |
| abstractText | Inflammasomes are multiprotein complexes that coordinate cellular inflammatory responses and mediate host defense. Following recognition of pathogens and danger signals, inflammasomes assemble and recruit and activate caspase-1, the cysteine protease that cleaves numerous downstream targets, including pro-IL-1beta and pro-IL-18 into their biologically active form. In this study, we sought to develop a biosensor that would allow us to monitor the initiation, progression, and resolution of inflammation in living animals. To this end, we inserted a known caspase-1 target sequence into a circularly permuted luciferase construct that becomes bioluminescent upon protease cleavage. This biosensor was activated in response to various inflammatory stimuli in human monocytic cell lines and murine bone marrow-derived macrophages. Next, we generated C57BL/6 transgenic mice constitutively expressing the caspase-1 biosensor. We were able to monitor the spatiotemporal dynamics of caspase-1 activation and onset of inflammation in individual animals in the context of a systemic bacterial infection, colitis, and acute graft-versus-host disease. These data established a model whereby the development and progression of inflammatory responses can be monitored in the context of these and other mouse models of disease. |
