Article abstract
Nature Immunology 9, 857 - 865 (2008)
Published online: 11 July 2008 | doi:10.1038/ni.1636
The NALP3 inflammasome is involved in the innate immune response to amyloid-
Annett Halle1, Veit Hornung1, Gabor C Petzold2, Cameron R Stewart3, Brian G Monks1, Thomas Reinheckel4, Katherine A Fitzgerald1, Eicke Latz1, Kathryn J Moore3 & Douglas T Golenbock1
Abstract
The fibrillar peptide amyloid-
(A) has a chief function in the pathogenesis of Alzheimer's disease. Interleukin 1 (IL-1) is a key cytokine in the inflammatory response to A. Insoluble materials such as crystals activate the inflammasome formed by the cytoplasmic receptor NALP3, which results in the release of IL-1. Here we identify the NALP3 inflammasome as a sensor of A in a process involving the phagocytosis of A and subsequent lysosomal damage and release of cathepsin B. Furthermore, the IL-1 pathway was essential for the microglial synthesis of proinflammatory and neurotoxic factors, and the inflammasome, caspase-1 and IL-1 were critical for the recruitment of microglia to exogenous A in the brain. Our findings suggest that activation of the NALP3 inflammasome is important for inflammation and tissue damage in Alzheimer's disease.
- Department of Infectious Diseases and Immunology, University of Massachusetts Medical School, Worcester, Massachusetts 01605, USA.
- Center for Brain Science and Department of Molecular and Cellular Biology, Harvard University, Cambridge, Massachusetts 02138, USA.
- Lipid Metabolism Unit, Massachusetts General Hospital, Harvard Medical School, Boston, Massachusetts 02114, USA.
- Institute for Molecular Medicine und Cell Research, Albert-Ludwigs University, Freiburg 79104, Germany.
Correspondence to: Douglas T Golenbock1 e-mail: douglas.golenbock@umassmed.edu
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