Cargando…

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,...

Descripción completa

Detalles Bibliográficos
Autores principales: Ghonime, Mohammed G., Mitra, Srabani, Eldomany, Ramadan A., Wewers, Mark D., Gavrilin, Mikhail A.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Public Library of Science 2015
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
_version_ 1782372044647694336
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
work_keys_str_mv AT ghonimemohammedg inflammasomeprimingissimilarforfrancisellaspeciesthatdifferentiallyinduceinflammasomeactivation
AT mitrasrabani inflammasomeprimingissimilarforfrancisellaspeciesthatdifferentiallyinduceinflammasomeactivation
AT eldomanyramadana inflammasomeprimingissimilarforfrancisellaspeciesthatdifferentiallyinduceinflammasomeactivation
AT wewersmarkd inflammasomeprimingissimilarforfrancisellaspeciesthatdifferentiallyinduceinflammasomeactivation
AT gavrilinmikhaila inflammasomeprimingissimilarforfrancisellaspeciesthatdifferentiallyinduceinflammasomeactivation