Journal article
NLRP1 Inflammasome Activation Induces Pyroptosis of Hematopoietic Progenitor Cells
SL Masters, M Gerlic, D Metcalf, S Preston, M Pellegrini, JA O'Donnell, K McArthur, TM Baldwin, S Chevrier, CJ Nowell, LH Cengia, KJ Henley, JE Collinge, DL Kastner, L Feigenbaum, DJ Hilton, WS Alexander, BT Kile, BA Croker
Immunity | CELL PRESS | Published : 2012
Abstract
Cytopenias are key prognostic indicators of life-threatening infection, contributing to immunosuppression and mortality. Here we define a role for Caspase-1-dependent death, known as pyroptosis, in infection-induced cytopenias by studying inflammasome activation in hematopoietic progenitor cells. The NLRP1a inflammasome is expressed in hematopoietic progenitor cells and its activation triggers their pyroptotic death. Active NLRP1a induced a lethal systemic inflammatory disease that was driven by Caspase-1 and IL-1β but was independent of apoptosis-associated speck-like protein containing a CARD (ASC) and ameliorated by IL-18. Surprisingly, in the absence of IL-1β-driven inflammation, active ..
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Awarded by National Institute of Arthritis and Musculoskeletal and Skin Diseases
Funding Acknowledgements
We thank S. Mifsud, L. DiRago, and J. Corbin for excellent technical assistance and E. Lanera, S. Ross, S. Guzzardi, S. Brown, E. Salt, and M. Salzone for outstanding animal husbandry. We thank V. Dixit for Caspase-11-deficient mice. This work was supported by Project Grants (637367, 1002426), a Program Grant (461219), Fellowships (B.A.C., D.J.H., W.S.A., S.L.M., B.T.K.), and an Independent Research Institutes Infrastructure Support Scheme Grant (361646) from the Australian National Health and Medical Research Council (NHMRC); Fellowships from the Australian Research Council (B.A.C., B.T.K.), the Sylvia and Charles Viertel Foundation (B.T.K.), and the Cancer Council of Victoria (D.M.); the Australian Cancer Research Fund; the Australian Phenomics Network; and a Victorian State Government Operational Infrastructure Support Grant.