Abstract
Many chronic liver disorders are characterized by dysregulated immune responses and hepatocyte death. We used an in vivo model to study the immune response to necrotic liver injury and found that necrotic liver cells induced eosinophil recruitment. Necrotic liver induced eosinophil IL-1β and IL-18 secretion, degranulation, and cell death. Caspase-1 inhibitors blocked all of these responses. Caspase-1–mediated cell death with accompanying cytokine release is the hallmark of a novel form of cell death termed pyroptosis. To confirm this response in a disease model, we isolated eosinophils from the livers of Schistosoma mansoni–infected mice. S. mansoni eggs lodge in the hepatic sinusoids of infected mice, resulting in hepatocyte death, inflammation, and progressive liver fibrosis. This response is typified by massive eosinophilia, and we were able to confirm pyroptosis in the infiltrating eosinophils. This demonstrated that pyroptosis is a cellular pathway used by eosinophils in response to large-scale hepatic cell death.
Footnotes
This work was supported by MedImmune, the global biologics research and development arm of AstraZeneca. T.A.W. is supported by the Intramural Research Program of the National Institutes of Health/National Institute of Allergy and Infectious Diseases.
The online version of this article contains supplemental material.
- Received July 25, 2016.
- Accepted June 5, 2017.
- Copyright © 2017 by The American Association of Immunologists, Inc.