Early apoptosis of macrophages modulated by injection of Yersinia pestis YopK promotes progression of primary pneumonic plague.

Yersinia pestis causes pneumonic plague, a disease characterized by inflammation, necrosis and rapid bacterial growth which together cause acute lung congestion and lethality. The bacterial type III secretion system (T3SS) injects 7 effector proteins into host cells and their combined activities are...

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Autores principales:	Kristen N Peters, Miqdad O Dhariwala, Jennifer M Hughes Hanks, Charles R Brown, Deborah M Anderson
Formato:	article
Lenguaje:	EN
Publicado:	Public Library of Science (PLoS) 2013
Materias:	Immunologic diseases. Allergy RC581-607 Biology (General) QH301-705.5
Acceso en línea:	https://doaj.org/article/a6383037d7634f3e89e1a299cb124e26
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spelling	oai:doaj.org-article:a6383037d7634f3e89e1a299cb124e262021-11-18T06:05:43ZEarly apoptosis of macrophages modulated by injection of Yersinia pestis YopK promotes progression of primary pneumonic plague.1553-73661553-737410.1371/journal.ppat.1003324https://doaj.org/article/a6383037d7634f3e89e1a299cb124e262013-01-01T00:00:00Zhttps://www.ncbi.nlm.nih.gov/pmc/articles/pmid/23633954/pdf/?tool=EBIhttps://doaj.org/toc/1553-7366https://doaj.org/toc/1553-7374Yersinia pestis causes pneumonic plague, a disease characterized by inflammation, necrosis and rapid bacterial growth which together cause acute lung congestion and lethality. The bacterial type III secretion system (T3SS) injects 7 effector proteins into host cells and their combined activities are necessary to establish infection. Y. pestis infection of the lungs proceeds as a biphasic inflammatory response believed to be regulated through the control of apoptosis and pyroptosis by a single, well-conserved T3SS effector protein YopJ. Recently, YopJ-mediated pyroptosis, which proceeds via the NLRP3-inflammasome, was shown to be regulated by a second T3SS effector protein YopK in the related strain Y. pseudotuberculosis. In this work, we show that for Y. pestis, YopK appears to regulate YopJ-mediated apoptosis, rather than pyroptosis, of macrophages. Inhibition of caspase-8 blocked YopK-dependent apoptosis, suggesting the involvement of the extrinsic pathway, and appeared cell-type specific. However, in contrast to yopJ, deletion of yopK caused a large decrease in virulence in a mouse pneumonic plague model. YopK-dependent modulation of macrophage apoptosis was observed at 6 and 24 hours post-infection (HPI). When YopK was absent, decreased populations of macrophages and dendritic cells were seen in the lungs at 24 HPI and correlated with resolution rather than progression of inflammation. Together the data suggest that Y. pestis YopK may coordinate the inflammatory response during pneumonic plague through the regulation of apoptosis of immune cells.Kristen N PetersMiqdad O DhariwalaJennifer M Hughes HanksCharles R BrownDeborah M AndersonPublic Library of Science (PLoS)articleImmunologic diseases. AllergyRC581-607Biology (General)QH301-705.5ENPLoS Pathogens, Vol 9, Iss 4, p e1003324 (2013)
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 Kristen N Peters Miqdad O Dhariwala Jennifer M Hughes Hanks Charles R Brown Deborah M Anderson Early apoptosis of macrophages modulated by injection of Yersinia pestis YopK promotes progression of primary pneumonic plague.
description	Yersinia pestis causes pneumonic plague, a disease characterized by inflammation, necrosis and rapid bacterial growth which together cause acute lung congestion and lethality. The bacterial type III secretion system (T3SS) injects 7 effector proteins into host cells and their combined activities are necessary to establish infection. Y. pestis infection of the lungs proceeds as a biphasic inflammatory response believed to be regulated through the control of apoptosis and pyroptosis by a single, well-conserved T3SS effector protein YopJ. Recently, YopJ-mediated pyroptosis, which proceeds via the NLRP3-inflammasome, was shown to be regulated by a second T3SS effector protein YopK in the related strain Y. pseudotuberculosis. In this work, we show that for Y. pestis, YopK appears to regulate YopJ-mediated apoptosis, rather than pyroptosis, of macrophages. Inhibition of caspase-8 blocked YopK-dependent apoptosis, suggesting the involvement of the extrinsic pathway, and appeared cell-type specific. However, in contrast to yopJ, deletion of yopK caused a large decrease in virulence in a mouse pneumonic plague model. YopK-dependent modulation of macrophage apoptosis was observed at 6 and 24 hours post-infection (HPI). When YopK was absent, decreased populations of macrophages and dendritic cells were seen in the lungs at 24 HPI and correlated with resolution rather than progression of inflammation. Together the data suggest that Y. pestis YopK may coordinate the inflammatory response during pneumonic plague through the regulation of apoptosis of immune cells.
format	article
author	Kristen N Peters Miqdad O Dhariwala Jennifer M Hughes Hanks Charles R Brown Deborah M Anderson
author_facet	Kristen N Peters Miqdad O Dhariwala Jennifer M Hughes Hanks Charles R Brown Deborah M Anderson
author_sort	Kristen N Peters
title	Early apoptosis of macrophages modulated by injection of Yersinia pestis YopK promotes progression of primary pneumonic plague.
title_short	Early apoptosis of macrophages modulated by injection of Yersinia pestis YopK promotes progression of primary pneumonic plague.
title_full	Early apoptosis of macrophages modulated by injection of Yersinia pestis YopK promotes progression of primary pneumonic plague.
title_fullStr	Early apoptosis of macrophages modulated by injection of Yersinia pestis YopK promotes progression of primary pneumonic plague.
title_full_unstemmed	Early apoptosis of macrophages modulated by injection of Yersinia pestis YopK promotes progression of primary pneumonic plague.
title_sort	early apoptosis of macrophages modulated by injection of yersinia pestis yopk promotes progression of primary pneumonic plague.
publisher	Public Library of Science (PLoS)
publishDate	2013
url	https://doaj.org/article/a6383037d7634f3e89e1a299cb124e26
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Early apoptosis of macrophages modulated by injection of Yersinia pestis YopK promotes progression of primary pneumonic plague.

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