Sponsor
The following funding sources supported the research reported in this manuscript: NIAID, United States 1R01 AI109539, NIAID, United States 2R01 AI095396-06, NIGMS, United States T32GM007276, NIAID, United States 5T32AI00729035, Dean's Postdoctoral Fellowship— Stanford School of Medicine, Stanford Graduate Fellowship—Gabilan Fellow, Allen Stanford Discovery Center Grant to D.M.M. from the Paul Allen Family Foundation.
Published In
iScience
Document Type
Article
Publication Date
9-29-2020
Subjects
Cellular control mechanisms, Endotoxins, Carrier proteins, Macrophages, Inflammation -- Pathophysiology, Binding proteins
Abstract
In mammalian cells, inflammatory caspases detect Gram-negative bacterial invasion by binding lipopolysaccharides (LPS). Murine caspase-11 binds cytosolic LPS, stimulates pyroptotic cell death, and drives sepsis pathogenesis. Extracellular priming factors enhance caspase-11-dependent pyroptosis. Herein we compare priming agents and demonstrate that IFNγ priming elicits the most rapid and amplified macrophage response to cytosolic LPS. Previous studies indicate that IFN-induced expression of caspase-11 and guanylate binding proteins (GBPs) are causal events explaining the effects of priming on cytosolic LPS sensing. We demonstrate that these events cannot fully account for the increased response triggered by IFNγ treatment. Indeed, IFNγ priming elicits higher pyroptosis levels in response to cytosolic LPS when macrophages stably express caspase-11. In macrophages lacking GBPs encoded on chromosome 3, IFNγ priming enhanced pyroptosis in response to cytosolic LPS as compared with other priming agents. These results suggest an unknown regulator of caspase-11-dependent pyroptosis exists, whose activity is upregulated by IFNγ.
Rights
© 2020 The Authors.
This work is licensed under a Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International License.
Locate the Document
DOI
10.1016/j.isci.2020.101612
Persistent Identifier
https://archives.pdx.edu/ds/psu/34272
Citation Details
Brubaker, S. W., Brewer, S. M., Massis, L. M., Napier, B. A., & Monack, D. M. (2020). A Rapid Caspase-11 Response Induced by IFNγ Priming Is Independent of Guanylate Binding Proteins. Iscience, 23(10), 101612.