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Pyroptosis triggers pore-induced intracellular traps (PITs) that capture bacteria and lead to their clearance by efferocytosis

Inflammasomes activate caspase-1 in response to cytosolic contamination or perturbation. This inflammatory caspase triggers the opening of the GSDMD pore in the plasma membrane, resulting in lytic cell death called pyroptosis. We had previously assumed that pyroptosis releases intracellular bacteria...

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Autores principales: Jorgensen, Ine, Zhang, Yue, Krantz, Bryan A., Miao, Edward A.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: The Rockefeller University Press 2016
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5030797/
https://www.ncbi.nlm.nih.gov/pubmed/27573815
http://dx.doi.org/10.1084/jem.20151613
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author Jorgensen, Ine
Zhang, Yue
Krantz, Bryan A.
Miao, Edward A.
author_facet Jorgensen, Ine
Zhang, Yue
Krantz, Bryan A.
Miao, Edward A.
author_sort Jorgensen, Ine
collection PubMed
description Inflammasomes activate caspase-1 in response to cytosolic contamination or perturbation. This inflammatory caspase triggers the opening of the GSDMD pore in the plasma membrane, resulting in lytic cell death called pyroptosis. We had previously assumed that pyroptosis releases intracellular bacteria to the extracellular space. Here, we find that viable bacteria instead remain trapped within the cellular debris of pyroptotic macrophages. This trapping appears to be an inevitable consequence of how osmotic lysis ruptures the plasma membrane, and may also apply to necroptosis and some forms of nonprogrammed necrosis. Although membrane tears release soluble cytosolic contents, they are small enough to retain organelles and bacteria. We call this structure the pore-induced intracellular trap (PIT), which is conceptually parallel to the neutrophil extracellular trap (NET). The PIT coordinates innate immune responses via complement and scavenger receptors to drive recruitment of and efferocytosis by neutrophils. Ultimately, this secondary phagocyte kills the bacteria. Hence, caspase-1–driven pore-induced cell death triggers a multifaceted defense against intracellular bacteria facilitated by trapping the pathogen within the cellular debris. Bona fide intracellular bacterial pathogens, such as Salmonella, must prevent or delay pyroptosis to avoid being trapped in the PIT and subsequently killed by neutrophils.
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spelling pubmed-50307972017-03-19 Pyroptosis triggers pore-induced intracellular traps (PITs) that capture bacteria and lead to their clearance by efferocytosis Jorgensen, Ine Zhang, Yue Krantz, Bryan A. Miao, Edward A. J Exp Med Research Articles Inflammasomes activate caspase-1 in response to cytosolic contamination or perturbation. This inflammatory caspase triggers the opening of the GSDMD pore in the plasma membrane, resulting in lytic cell death called pyroptosis. We had previously assumed that pyroptosis releases intracellular bacteria to the extracellular space. Here, we find that viable bacteria instead remain trapped within the cellular debris of pyroptotic macrophages. This trapping appears to be an inevitable consequence of how osmotic lysis ruptures the plasma membrane, and may also apply to necroptosis and some forms of nonprogrammed necrosis. Although membrane tears release soluble cytosolic contents, they are small enough to retain organelles and bacteria. We call this structure the pore-induced intracellular trap (PIT), which is conceptually parallel to the neutrophil extracellular trap (NET). The PIT coordinates innate immune responses via complement and scavenger receptors to drive recruitment of and efferocytosis by neutrophils. Ultimately, this secondary phagocyte kills the bacteria. Hence, caspase-1–driven pore-induced cell death triggers a multifaceted defense against intracellular bacteria facilitated by trapping the pathogen within the cellular debris. Bona fide intracellular bacterial pathogens, such as Salmonella, must prevent or delay pyroptosis to avoid being trapped in the PIT and subsequently killed by neutrophils. The Rockefeller University Press 2016-09-19 /pmc/articles/PMC5030797/ /pubmed/27573815 http://dx.doi.org/10.1084/jem.20151613 Text en © 2016 Jorgensen et al. This article is distributed under the terms of an Attribution–Noncommercial–Share Alike–No Mirror Sites license for the first six months after the publication date (see http://www.rupress.org/terms). After six months it is available under a Creative Commons License (Attribution–Noncommercial–Share Alike 3.0 Unported license, as described at http://creativecommons.org/licenses/by-nc-sa/3.0/).
spellingShingle Research Articles
Jorgensen, Ine
Zhang, Yue
Krantz, Bryan A.
Miao, Edward A.
Pyroptosis triggers pore-induced intracellular traps (PITs) that capture bacteria and lead to their clearance by efferocytosis
title Pyroptosis triggers pore-induced intracellular traps (PITs) that capture bacteria and lead to their clearance by efferocytosis
title_full Pyroptosis triggers pore-induced intracellular traps (PITs) that capture bacteria and lead to their clearance by efferocytosis
title_fullStr Pyroptosis triggers pore-induced intracellular traps (PITs) that capture bacteria and lead to their clearance by efferocytosis
title_full_unstemmed Pyroptosis triggers pore-induced intracellular traps (PITs) that capture bacteria and lead to their clearance by efferocytosis
title_short Pyroptosis triggers pore-induced intracellular traps (PITs) that capture bacteria and lead to their clearance by efferocytosis
title_sort pyroptosis triggers pore-induced intracellular traps (pits) that capture bacteria and lead to their clearance by efferocytosis
topic Research Articles
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5030797/
https://www.ncbi.nlm.nih.gov/pubmed/27573815
http://dx.doi.org/10.1084/jem.20151613
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