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A Rapid Caspase-11 Response Induced by IFNγ Priming Is Independent of Guanylate Binding Proteins

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. Here...

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Detalles Bibliográficos
Autores principales: Brubaker, Sky W., Brewer, Susan M., Massis, Liliana M., Napier, Brooke A., Monack, Denise M.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Elsevier 2020
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7566093/
https://www.ncbi.nlm.nih.gov/pubmed/33089101
http://dx.doi.org/10.1016/j.isci.2020.101612
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author Brubaker, Sky W.
Brewer, Susan M.
Massis, Liliana M.
Napier, Brooke A.
Monack, Denise M.
author_facet Brubaker, Sky W.
Brewer, Susan M.
Massis, Liliana M.
Napier, Brooke A.
Monack, Denise M.
author_sort Brubaker, Sky W.
collection PubMed
description 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.
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spelling pubmed-75660932020-10-20 A Rapid Caspase-11 Response Induced by IFNγ Priming Is Independent of Guanylate Binding Proteins Brubaker, Sky W. Brewer, Susan M. Massis, Liliana M. Napier, Brooke A. Monack, Denise M. iScience Article 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. Elsevier 2020-09-29 /pmc/articles/PMC7566093/ /pubmed/33089101 http://dx.doi.org/10.1016/j.isci.2020.101612 Text en © 2020 The Authors http://creativecommons.org/licenses/by-nc-nd/4.0/ This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/).
spellingShingle Article
Brubaker, Sky W.
Brewer, Susan M.
Massis, Liliana M.
Napier, Brooke A.
Monack, Denise M.
A Rapid Caspase-11 Response Induced by IFNγ Priming Is Independent of Guanylate Binding Proteins
title A Rapid Caspase-11 Response Induced by IFNγ Priming Is Independent of Guanylate Binding Proteins
title_full A Rapid Caspase-11 Response Induced by IFNγ Priming Is Independent of Guanylate Binding Proteins
title_fullStr A Rapid Caspase-11 Response Induced by IFNγ Priming Is Independent of Guanylate Binding Proteins
title_full_unstemmed A Rapid Caspase-11 Response Induced by IFNγ Priming Is Independent of Guanylate Binding Proteins
title_short A Rapid Caspase-11 Response Induced by IFNγ Priming Is Independent of Guanylate Binding Proteins
title_sort rapid caspase-11 response induced by ifnγ priming is independent of guanylate binding proteins
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7566093/
https://www.ncbi.nlm.nih.gov/pubmed/33089101
http://dx.doi.org/10.1016/j.isci.2020.101612
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