Caspase-7 activation by the Nlrc4/Ipaf inflammasome restricts Legionella pneumophila infection.

Legionella pneumophila (L. pneumophila), the causative agent of a severe form of pneumonia called Legionnaires' disease, replicates in human monocytes and macrophages. Most inbred mouse strains are restrictive to L. pneumophila infection except for the A/J, Nlrc4(-/-) (Ipaf(-/-)), and caspase-1...

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Autores principales:	Anwari Akhter, Mikhail A Gavrilin, Laura Frantz, Songcerae Washington, Cameron Ditty, Dominique Limoli, Colby Day, Anasuya Sarkar, Christie Newland, Jonathan Butchar, Clay B Marsh, Mark D Wewers, Susheela Tridandapani, Thirumala-Devi Kanneganti, Amal O Amer
Formato:	article
Lenguaje:	EN
Publicado:	Public Library of Science (PLoS) 2009
Materias:	Immunologic diseases. Allergy RC581-607 Biology (General) QH301-705.5
Acceso en línea:	https://doaj.org/article/c8897397390641b9852ccea43588c3f0
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spelling	oai:doaj.org-article:c8897397390641b9852ccea43588c3f02021-11-25T05:47:09ZCaspase-7 activation by the Nlrc4/Ipaf inflammasome restricts Legionella pneumophila infection.1553-73661553-737410.1371/journal.ppat.1000361https://doaj.org/article/c8897397390641b9852ccea43588c3f02009-04-01T00:00:00Zhttps://www.ncbi.nlm.nih.gov/pmc/articles/pmid/19343209/pdf/?tool=EBIhttps://doaj.org/toc/1553-7366https://doaj.org/toc/1553-7374Legionella pneumophila (L. pneumophila), the causative agent of a severe form of pneumonia called Legionnaires' disease, replicates in human monocytes and macrophages. Most inbred mouse strains are restrictive to L. pneumophila infection except for the A/J, Nlrc4(-/-) (Ipaf(-/-)), and caspase-1(-/-) derived macrophages. Particularly, caspase-1 activation is detected during L. pneumophila infection of murine macrophages while absent in human cells. Recent in vitro experiments demonstrate that caspase-7 is cleaved by caspase-1. However, the biological role for caspase-7 activation downstream of caspase-1 is not known. Furthermore, whether this reaction is pertinent to the apoptosis or to the inflammation pathway or whether it mediates a yet unidentified effect is unclear. Using the intracellular pathogen L. pneumophila, we show that, upon infection of murine macrophages, caspase-7 was activated downstream of the Nlrc4 inflammasome and required caspase-1 activation. Such activation of caspase-7 was mediated by flagellin and required a functional Naip5. Remarkably, mice lacking caspase-7 and its macrophages allowed substantial L. pneumophila replication. Permissiveness of caspase-7(-/-) macrophages to the intracellular pathogen was due to defective delivery of the organism to the lysosome and to delayed cell death during early stages of infection. These results reveal a new mechanism for caspase-7 activation downstream of the Nlrc4 inflammasome and present a novel biological role for caspase-7 in host defense against an intracellular bacterium.Anwari AkhterMikhail A GavrilinLaura FrantzSongcerae WashingtonCameron DittyDominique LimoliColby DayAnasuya SarkarChristie NewlandJonathan ButcharClay B MarshMark D WewersSusheela TridandapaniThirumala-Devi KannegantiAmal O AmerPublic Library of Science (PLoS)articleImmunologic diseases. AllergyRC581-607Biology (General)QH301-705.5ENPLoS Pathogens, Vol 5, Iss 4, p e1000361 (2009)
institution	DOAJ
collection	DOAJ
language	EN
topic	Immunologic diseases. Allergy RC581-607 Biology (General) QH301-705.5
spellingShingle	Immunologic diseases. Allergy RC581-607 Biology (General) QH301-705.5 Anwari Akhter Mikhail A Gavrilin Laura Frantz Songcerae Washington Cameron Ditty Dominique Limoli Colby Day Anasuya Sarkar Christie Newland Jonathan Butchar Clay B Marsh Mark D Wewers Susheela Tridandapani Thirumala-Devi Kanneganti Amal O Amer Caspase-7 activation by the Nlrc4/Ipaf inflammasome restricts Legionella pneumophila infection.
description	Legionella pneumophila (L. pneumophila), the causative agent of a severe form of pneumonia called Legionnaires' disease, replicates in human monocytes and macrophages. Most inbred mouse strains are restrictive to L. pneumophila infection except for the A/J, Nlrc4(-/-) (Ipaf(-/-)), and caspase-1(-/-) derived macrophages. Particularly, caspase-1 activation is detected during L. pneumophila infection of murine macrophages while absent in human cells. Recent in vitro experiments demonstrate that caspase-7 is cleaved by caspase-1. However, the biological role for caspase-7 activation downstream of caspase-1 is not known. Furthermore, whether this reaction is pertinent to the apoptosis or to the inflammation pathway or whether it mediates a yet unidentified effect is unclear. Using the intracellular pathogen L. pneumophila, we show that, upon infection of murine macrophages, caspase-7 was activated downstream of the Nlrc4 inflammasome and required caspase-1 activation. Such activation of caspase-7 was mediated by flagellin and required a functional Naip5. Remarkably, mice lacking caspase-7 and its macrophages allowed substantial L. pneumophila replication. Permissiveness of caspase-7(-/-) macrophages to the intracellular pathogen was due to defective delivery of the organism to the lysosome and to delayed cell death during early stages of infection. These results reveal a new mechanism for caspase-7 activation downstream of the Nlrc4 inflammasome and present a novel biological role for caspase-7 in host defense against an intracellular bacterium.
format	article
author	Anwari Akhter Mikhail A Gavrilin Laura Frantz Songcerae Washington Cameron Ditty Dominique Limoli Colby Day Anasuya Sarkar Christie Newland Jonathan Butchar Clay B Marsh Mark D Wewers Susheela Tridandapani Thirumala-Devi Kanneganti Amal O Amer
author_facet	Anwari Akhter Mikhail A Gavrilin Laura Frantz Songcerae Washington Cameron Ditty Dominique Limoli Colby Day Anasuya Sarkar Christie Newland Jonathan Butchar Clay B Marsh Mark D Wewers Susheela Tridandapani Thirumala-Devi Kanneganti Amal O Amer
author_sort	Anwari Akhter
title	Caspase-7 activation by the Nlrc4/Ipaf inflammasome restricts Legionella pneumophila infection.
title_short	Caspase-7 activation by the Nlrc4/Ipaf inflammasome restricts Legionella pneumophila infection.
title_full	Caspase-7 activation by the Nlrc4/Ipaf inflammasome restricts Legionella pneumophila infection.
title_fullStr	Caspase-7 activation by the Nlrc4/Ipaf inflammasome restricts Legionella pneumophila infection.
title_full_unstemmed	Caspase-7 activation by the Nlrc4/Ipaf inflammasome restricts Legionella pneumophila infection.
title_sort	caspase-7 activation by the nlrc4/ipaf inflammasome restricts legionella pneumophila infection.
publisher	Public Library of Science (PLoS)
publishDate	2009
url	https://doaj.org/article/c8897397390641b9852ccea43588c3f0
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Caspase-7 activation by the Nlrc4/Ipaf inflammasome restricts Legionella pneumophila infection.

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