Salmonella typhimurium-induced IL-1 release from primary human monocytes requires NLRP3 and can occur in the absence of pyroptosis

Abstract Large molecular complexes known as inflammasomes regulate the release of IL-1β from immune cells in response to infection and injury. Salmonella typhimurium infection is reported to activate NLRP3 and NLRC4 inflammasomes which are subsequently involved in pyroptosis of the cell and pathogen...

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Autores principales:	Catherine E. Diamond, Keith Weng Kit Leong, Maurizio Vacca, Jack Rivers-Auty, David Brough, Alessandra Mortellaro
Formato:	article
Lenguaje:	EN
Publicado:	Nature Portfolio 2017
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/96a171536d414f1bb88d3ce44874359c
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spelling	oai:doaj.org-article:96a171536d414f1bb88d3ce44874359c2021-12-02T11:53:05ZSalmonella typhimurium-induced IL-1 release from primary human monocytes requires NLRP3 and can occur in the absence of pyroptosis10.1038/s41598-017-07081-32045-2322https://doaj.org/article/96a171536d414f1bb88d3ce44874359c2017-07-01T00:00:00Zhttps://doi.org/10.1038/s41598-017-07081-3https://doaj.org/toc/2045-2322Abstract Large molecular complexes known as inflammasomes regulate the release of IL-1β from immune cells in response to infection and injury. Salmonella typhimurium infection is reported to activate NLRP3 and NLRC4 inflammasomes which are subsequently involved in pyroptosis of the cell and pathogen clearance. However, the response to S. typhimurium in primary human monocytes has not been studied in detail. The aim of this study was to investigate the effect of S. typhimurium on inflammasomes in primary human monocytes. Much of the previous research in the field has been conducted in murine models and human THP-1 cells, which may not reflect the responses of primary human monocytes. Here, we report that inhibiting NLRP3 with the selective inhibitor MCC950, blocked release of IL-1β and the related cytokine IL-1α from primary human monocytes in response to S. typhimurium. Additionally, under these conditions S. typhimurium-induced IL-1 release occurred independently of pyroptosis. We propose that IL-1β release without pyroptosis may occur in early-recruited monocytes to regulate a maximal innate immune response to Salmonella infection, allowing a sustained inflammatory signal. This insight into the mechanisms involved in IL-1 release from primary human monocytes highlights major differences between immune cell types, and the defences they employ during bacterial infection.Catherine E. DiamondKeith Weng Kit LeongMaurizio VaccaJack Rivers-AutyDavid BroughAlessandra MortellaroNature PortfolioarticleMedicineRScienceQENScientific Reports, Vol 7, Iss 1, Pp 1-9 (2017)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Catherine E. Diamond Keith Weng Kit Leong Maurizio Vacca Jack Rivers-Auty David Brough Alessandra Mortellaro Salmonella typhimurium-induced IL-1 release from primary human monocytes requires NLRP3 and can occur in the absence of pyroptosis
description	Abstract Large molecular complexes known as inflammasomes regulate the release of IL-1β from immune cells in response to infection and injury. Salmonella typhimurium infection is reported to activate NLRP3 and NLRC4 inflammasomes which are subsequently involved in pyroptosis of the cell and pathogen clearance. However, the response to S. typhimurium in primary human monocytes has not been studied in detail. The aim of this study was to investigate the effect of S. typhimurium on inflammasomes in primary human monocytes. Much of the previous research in the field has been conducted in murine models and human THP-1 cells, which may not reflect the responses of primary human monocytes. Here, we report that inhibiting NLRP3 with the selective inhibitor MCC950, blocked release of IL-1β and the related cytokine IL-1α from primary human monocytes in response to S. typhimurium. Additionally, under these conditions S. typhimurium-induced IL-1 release occurred independently of pyroptosis. We propose that IL-1β release without pyroptosis may occur in early-recruited monocytes to regulate a maximal innate immune response to Salmonella infection, allowing a sustained inflammatory signal. This insight into the mechanisms involved in IL-1 release from primary human monocytes highlights major differences between immune cell types, and the defences they employ during bacterial infection.
format	article
author	Catherine E. Diamond Keith Weng Kit Leong Maurizio Vacca Jack Rivers-Auty David Brough Alessandra Mortellaro
author_facet	Catherine E. Diamond Keith Weng Kit Leong Maurizio Vacca Jack Rivers-Auty David Brough Alessandra Mortellaro
author_sort	Catherine E. Diamond
title	Salmonella typhimurium-induced IL-1 release from primary human monocytes requires NLRP3 and can occur in the absence of pyroptosis
title_short	Salmonella typhimurium-induced IL-1 release from primary human monocytes requires NLRP3 and can occur in the absence of pyroptosis
title_full	Salmonella typhimurium-induced IL-1 release from primary human monocytes requires NLRP3 and can occur in the absence of pyroptosis
title_fullStr	Salmonella typhimurium-induced IL-1 release from primary human monocytes requires NLRP3 and can occur in the absence of pyroptosis
title_full_unstemmed	Salmonella typhimurium-induced IL-1 release from primary human monocytes requires NLRP3 and can occur in the absence of pyroptosis
title_sort	salmonella typhimurium-induced il-1 release from primary human monocytes requires nlrp3 and can occur in the absence of pyroptosis
publisher	Nature Portfolio
publishDate	2017
url	https://doaj.org/article/96a171536d414f1bb88d3ce44874359c
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Salmonella typhimurium-induced IL-1 release from primary human monocytes requires NLRP3 and can occur in the absence of pyroptosis

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