Cargando…
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...
Autores principales: | , , , , |
---|---|
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 |
_version_ | 1783596076151865344 |
---|---|
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. |
format | Online Article Text |
id | pubmed-7566093 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2020 |
publisher | Elsevier |
record_format | MEDLINE/PubMed |
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 |
work_keys_str_mv | AT brubakerskyw arapidcaspase11responseinducedbyifngprimingisindependentofguanylatebindingproteins AT brewersusanm arapidcaspase11responseinducedbyifngprimingisindependentofguanylatebindingproteins AT massislilianam arapidcaspase11responseinducedbyifngprimingisindependentofguanylatebindingproteins AT napierbrookea arapidcaspase11responseinducedbyifngprimingisindependentofguanylatebindingproteins AT monackdenisem arapidcaspase11responseinducedbyifngprimingisindependentofguanylatebindingproteins AT brubakerskyw rapidcaspase11responseinducedbyifngprimingisindependentofguanylatebindingproteins AT brewersusanm rapidcaspase11responseinducedbyifngprimingisindependentofguanylatebindingproteins AT massislilianam rapidcaspase11responseinducedbyifngprimingisindependentofguanylatebindingproteins AT napierbrookea rapidcaspase11responseinducedbyifngprimingisindependentofguanylatebindingproteins AT monackdenisem rapidcaspase11responseinducedbyifngprimingisindependentofguanylatebindingproteins |