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An NLRP3 inflammasome-triggered cytokine storm contributes to Streptococcal toxic shock-like syndrome (STSLS)

Infection with the Streptococcus suis (S. suis) epidemic strain can cause Streptococcal toxic shock-like syndrome (STSLS), which is characterized by a cytokine storm, dysfunction of multiple organs and a high incidence of mortality despite adequate treatment. Despite some progress concerning the con...

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Autores principales: Lin, Lan, Xu, Lei, Lv, Weihua, Han, Li, Xiang, Yaozu, Fu, Lei, Jin, Meilin, Zhou, Rui, Chen, Huanchun, Zhang, Anding
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Public Library of Science 2019
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6553798/
https://www.ncbi.nlm.nih.gov/pubmed/31170267
http://dx.doi.org/10.1371/journal.ppat.1007795
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author Lin, Lan
Xu, Lei
Lv, Weihua
Han, Li
Xiang, Yaozu
Fu, Lei
Jin, Meilin
Zhou, Rui
Chen, Huanchun
Zhang, Anding
author_facet Lin, Lan
Xu, Lei
Lv, Weihua
Han, Li
Xiang, Yaozu
Fu, Lei
Jin, Meilin
Zhou, Rui
Chen, Huanchun
Zhang, Anding
author_sort Lin, Lan
collection PubMed
description Infection with the Streptococcus suis (S. suis) epidemic strain can cause Streptococcal toxic shock-like syndrome (STSLS), which is characterized by a cytokine storm, dysfunction of multiple organs and a high incidence of mortality despite adequate treatment. Despite some progress concerning the contribution of the inflammatory response to STSLS, the precise mechanism underlying STSLS development remains elusive. Here, we use a murine model to demonstrate that caspase-1 activity is critical for STSLS development. Furthermore, we show that inflammasome activation by S. suis is mainly dependent on NLRP3 but not on NLRP1, AIM2 or NLRC4. The important role of NLRP3 activation in STSLS is further confirmed in vivo with the NLRP3 inhibitor MCC950 and nlrp3-knockout mice. By comparison of WT strain with isogenic strains with mutation of various virulence genes for inflammasome activation, Suilysin is essential for inflammasome activation, which is dependent on the membrane perforation activity to cause cytosolic K(+) efflux. Moreover, the mutant strain msly (P353L) expressing mutagenic SLY without hemolytic activity was unable to activate the inflammasome and does not cause STSLS. In summary, we demonstrate that the high membrane perforation activity of the epidemic strain induces a high level of NLRP3 inflammasome activation, which is essential for the development of the cytokine storm and multi-organ dysfunction in STSLS and suggests NLRP3 inflammasome as an attractive target for the treatment of STSLS.
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spelling pubmed-65537982019-06-17 An NLRP3 inflammasome-triggered cytokine storm contributes to Streptococcal toxic shock-like syndrome (STSLS) Lin, Lan Xu, Lei Lv, Weihua Han, Li Xiang, Yaozu Fu, Lei Jin, Meilin Zhou, Rui Chen, Huanchun Zhang, Anding PLoS Pathog Research Article Infection with the Streptococcus suis (S. suis) epidemic strain can cause Streptococcal toxic shock-like syndrome (STSLS), which is characterized by a cytokine storm, dysfunction of multiple organs and a high incidence of mortality despite adequate treatment. Despite some progress concerning the contribution of the inflammatory response to STSLS, the precise mechanism underlying STSLS development remains elusive. Here, we use a murine model to demonstrate that caspase-1 activity is critical for STSLS development. Furthermore, we show that inflammasome activation by S. suis is mainly dependent on NLRP3 but not on NLRP1, AIM2 or NLRC4. The important role of NLRP3 activation in STSLS is further confirmed in vivo with the NLRP3 inhibitor MCC950 and nlrp3-knockout mice. By comparison of WT strain with isogenic strains with mutation of various virulence genes for inflammasome activation, Suilysin is essential for inflammasome activation, which is dependent on the membrane perforation activity to cause cytosolic K(+) efflux. Moreover, the mutant strain msly (P353L) expressing mutagenic SLY without hemolytic activity was unable to activate the inflammasome and does not cause STSLS. In summary, we demonstrate that the high membrane perforation activity of the epidemic strain induces a high level of NLRP3 inflammasome activation, which is essential for the development of the cytokine storm and multi-organ dysfunction in STSLS and suggests NLRP3 inflammasome as an attractive target for the treatment of STSLS. Public Library of Science 2019-06-06 /pmc/articles/PMC6553798/ /pubmed/31170267 http://dx.doi.org/10.1371/journal.ppat.1007795 Text en © 2019 Lin 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 (http://creativecommons.org/licenses/by/4.0/) , which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
spellingShingle Research Article
Lin, Lan
Xu, Lei
Lv, Weihua
Han, Li
Xiang, Yaozu
Fu, Lei
Jin, Meilin
Zhou, Rui
Chen, Huanchun
Zhang, Anding
An NLRP3 inflammasome-triggered cytokine storm contributes to Streptococcal toxic shock-like syndrome (STSLS)
title An NLRP3 inflammasome-triggered cytokine storm contributes to Streptococcal toxic shock-like syndrome (STSLS)
title_full An NLRP3 inflammasome-triggered cytokine storm contributes to Streptococcal toxic shock-like syndrome (STSLS)
title_fullStr An NLRP3 inflammasome-triggered cytokine storm contributes to Streptococcal toxic shock-like syndrome (STSLS)
title_full_unstemmed An NLRP3 inflammasome-triggered cytokine storm contributes to Streptococcal toxic shock-like syndrome (STSLS)
title_short An NLRP3 inflammasome-triggered cytokine storm contributes to Streptococcal toxic shock-like syndrome (STSLS)
title_sort nlrp3 inflammasome-triggered cytokine storm contributes to streptococcal toxic shock-like syndrome (stsls)
topic Research Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6553798/
https://www.ncbi.nlm.nih.gov/pubmed/31170267
http://dx.doi.org/10.1371/journal.ppat.1007795
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