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Inflammasome Priming Is Similar for Francisella Species That Differentially Induce Inflammasome Activation
Inflammasome activation is a two-step process where step one, priming, prepares the inflammasome for its subsequent activation, by step two. Classically step one can be induced by LPS priming followed by step two, high dose ATP. Furthermore, when IL-18 processing is used as the inflammasome readout,...
Autores principales: | , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Public Library of Science
2015
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4436270/ https://www.ncbi.nlm.nih.gov/pubmed/25993107 http://dx.doi.org/10.1371/journal.pone.0127278 |
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author | Ghonime, Mohammed G. Mitra, Srabani Eldomany, Ramadan A. Wewers, Mark D. Gavrilin, Mikhail A. |
author_facet | Ghonime, Mohammed G. Mitra, Srabani Eldomany, Ramadan A. Wewers, Mark D. Gavrilin, Mikhail A. |
author_sort | Ghonime, Mohammed G. |
collection | PubMed |
description | Inflammasome activation is a two-step process where step one, priming, prepares the inflammasome for its subsequent activation, by step two. Classically step one can be induced by LPS priming followed by step two, high dose ATP. Furthermore, when IL-18 processing is used as the inflammasome readout, priming occurs before new protein synthesis. In this context, how intracellular pathogens such as Francisella activate the inflammasome is incompletely understood, particularly regarding the relative importance of priming versus activation steps. To better understand these events we compared Francisella strains that differ in virulence and ability to induce inflammasome activation for their relative effects on step one vs. step two. When using the rapid priming model, i.e., 30 min priming by live or heat killed Francisella strains (step 1), followed by ATP (step 2), we found no difference in IL-18 release, p20 caspase-1 release and ASC oligomerization between Francisella strains (F. novicida, F. holarctica –LVS and F. tularensis Schu S4). This priming is fast, independent of bacteria viability, internalization and phagosome escape, but requires TLR2-mediated ERK phosphorylation. In contrast to their efficient priming capacity, Francisella strains LVS and Schu S4 were impaired in inflammasome triggering compared to F. novicida. Thus, observed differences in inflammasome activation by F. novicida, LVS and Schu S4 depend not on differences in priming but rather on their propensity to trigger the primed inflammasome. |
format | Online Article Text |
id | pubmed-4436270 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2015 |
publisher | Public Library of Science |
record_format | MEDLINE/PubMed |
spelling | pubmed-44362702015-05-27 Inflammasome Priming Is Similar for Francisella Species That Differentially Induce Inflammasome Activation Ghonime, Mohammed G. Mitra, Srabani Eldomany, Ramadan A. Wewers, Mark D. Gavrilin, Mikhail A. PLoS One Research Article Inflammasome activation is a two-step process where step one, priming, prepares the inflammasome for its subsequent activation, by step two. Classically step one can be induced by LPS priming followed by step two, high dose ATP. Furthermore, when IL-18 processing is used as the inflammasome readout, priming occurs before new protein synthesis. In this context, how intracellular pathogens such as Francisella activate the inflammasome is incompletely understood, particularly regarding the relative importance of priming versus activation steps. To better understand these events we compared Francisella strains that differ in virulence and ability to induce inflammasome activation for their relative effects on step one vs. step two. When using the rapid priming model, i.e., 30 min priming by live or heat killed Francisella strains (step 1), followed by ATP (step 2), we found no difference in IL-18 release, p20 caspase-1 release and ASC oligomerization between Francisella strains (F. novicida, F. holarctica –LVS and F. tularensis Schu S4). This priming is fast, independent of bacteria viability, internalization and phagosome escape, but requires TLR2-mediated ERK phosphorylation. In contrast to their efficient priming capacity, Francisella strains LVS and Schu S4 were impaired in inflammasome triggering compared to F. novicida. Thus, observed differences in inflammasome activation by F. novicida, LVS and Schu S4 depend not on differences in priming but rather on their propensity to trigger the primed inflammasome. Public Library of Science 2015-05-18 /pmc/articles/PMC4436270/ /pubmed/25993107 http://dx.doi.org/10.1371/journal.pone.0127278 Text en © 2015 Ghonime et al http://creativecommons.org/licenses/by/4.0/ This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are properly credited. |
spellingShingle | Research Article Ghonime, Mohammed G. Mitra, Srabani Eldomany, Ramadan A. Wewers, Mark D. Gavrilin, Mikhail A. Inflammasome Priming Is Similar for Francisella Species That Differentially Induce Inflammasome Activation |
title | Inflammasome Priming Is Similar for Francisella Species That Differentially Induce Inflammasome Activation |
title_full | Inflammasome Priming Is Similar for Francisella Species That Differentially Induce Inflammasome Activation |
title_fullStr | Inflammasome Priming Is Similar for Francisella Species That Differentially Induce Inflammasome Activation |
title_full_unstemmed | Inflammasome Priming Is Similar for Francisella Species That Differentially Induce Inflammasome Activation |
title_short | Inflammasome Priming Is Similar for Francisella Species That Differentially Induce Inflammasome Activation |
title_sort | inflammasome priming is similar for francisella species that differentially induce inflammasome activation |
topic | Research Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4436270/ https://www.ncbi.nlm.nih.gov/pubmed/25993107 http://dx.doi.org/10.1371/journal.pone.0127278 |
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