Title |
Cutting Edge: The NLRP3 Inflammasome Links Complement-Mediated Inflammation and IL-1β Release
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Published in |
The Journal of Immunology, August 2013
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DOI | 10.4049/jimmunol.1300489 |
Pubmed ID | |
Authors |
Federica Laudisi, Roberto Spreafico, Maximilien Evrard, Timothy R. Hughes, Barbara Mandriani, Matheswaran Kandasamy, B. Paul Morgan, Baalasubramanian Sivasankar, Alessandra Mortellaro |
Abstract |
The complement system is a potent component of the innate immune response, promoting inflammation and orchestrating defense against pathogens. However, dysregulation of complement is critical to several autoimmune and inflammatory syndromes. Elevated expression of the proinflammatory cytokine IL-1β is often linked to such diseases. In this study, we reveal the mechanistic link between complement and IL-1β secretion using murine dendritic cells. IL-1β secretion occurs following intracellular caspase-1 activation by inflammasomes. We show that complement elicits secretion of both IL-1β and IL-18 in vitro and in vivo via the NLRP3 inflammasome. This effect depends on the inflammasome components NLRP3 and ASC, as well as caspase-1 activity. Interestingly, sublethal complement membrane attack complex formation, but not the anaphylatoxins C3a and C5a, activated the NLRP3 inflammasome in vivo. These findings provide insight into the molecular processes underlying complement-mediated inflammation and highlight the possibility of targeting IL-1β to control complement-induced disease and pathological inflammation. |
X Demographics
Geographical breakdown
Country | Count | As % |
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Unknown | 1 | 100% |
Demographic breakdown
Type | Count | As % |
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Members of the public | 1 | 100% |
Mendeley readers
Geographical breakdown
Country | Count | As % |
---|---|---|
Brazil | 3 | 2% |
Italy | 1 | <1% |
Canada | 1 | <1% |
Spain | 1 | <1% |
United States | 1 | <1% |
Unknown | 174 | 96% |
Demographic breakdown
Readers by professional status | Count | As % |
---|---|---|
Student > Ph. D. Student | 49 | 27% |
Researcher | 40 | 22% |
Student > Master | 20 | 11% |
Professor > Associate Professor | 8 | 4% |
Student > Bachelor | 7 | 4% |
Other | 25 | 14% |
Unknown | 32 | 18% |
Readers by discipline | Count | As % |
---|---|---|
Agricultural and Biological Sciences | 60 | 33% |
Immunology and Microbiology | 27 | 15% |
Medicine and Dentistry | 24 | 13% |
Biochemistry, Genetics and Molecular Biology | 14 | 8% |
Neuroscience | 5 | 3% |
Other | 9 | 5% |
Unknown | 42 | 23% |