Spatially Distinct Neutrophil Responses within the Inflammatory Lesions of Pneumonic Plague

ABSTRACT During pneumonic plague, the bacterium Yersinia pestis elicits the development of inflammatory lung lesions that continue to expand throughout infection. This lesion development and persistence are poorly understood. Here, we examine spatially distinct regions of lung lesions using laser ca...

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Autores principales:	Nikolas M. Stasulli, Kara R. Eichelberger, Paul A. Price, Roger D. Pechous, Stephanie A. Montgomery, Joel S. Parker, William E. Goldman
Formato:	article
Lenguaje:	EN
Publicado:	American Society for Microbiology 2015
Materias:	Microbiology QR1-502
Acceso en línea:	https://doaj.org/article/43c57dc31d544828a34444bf8f493d61
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spelling	oai:doaj.org-article:43c57dc31d544828a34444bf8f493d612021-11-15T15:41:31ZSpatially Distinct Neutrophil Responses within the Inflammatory Lesions of Pneumonic Plague10.1128/mBio.01530-152150-7511https://doaj.org/article/43c57dc31d544828a34444bf8f493d612015-10-01T00:00:00Zhttps://journals.asm.org/doi/10.1128/mBio.01530-15https://doaj.org/toc/2150-7511ABSTRACT During pneumonic plague, the bacterium Yersinia pestis elicits the development of inflammatory lung lesions that continue to expand throughout infection. This lesion development and persistence are poorly understood. Here, we examine spatially distinct regions of lung lesions using laser capture microdissection and transcriptome sequencing (RNA-seq) analysis to identify transcriptional differences between lesion microenvironments. We show that cellular pathways involved in leukocyte migration and apoptosis are downregulated in the center of lung lesions compared to the periphery. Probing for the bacterial factor(s) important for the alteration in neutrophil survival, we show both in vitro and in vivo that Y. pestis increases neutrophil survival in a manner that is dependent on the type III secretion system effector YopM. This research explores the complexity of spatially distinct host-microbe interactions and emphasizes the importance of cell relevance in assays in order to fully understand Y. pestis virulence. IMPORTANCE Yersinia pestis is a high-priority pathogen and continues to cause outbreaks worldwide. The ability of Y. pestis to be transmitted via respiratory droplets and its history of weaponization has led to its classification as a select agent most likely to be used as a biological weapon. Unrestricted bacterial growth during the initial preinflammatory phase primes patients to be infectious once disease symptoms begin in the proinflammatory phase, and the rapid disease progression can lead to death before Y. pestis infection can be diagnosed and treated. Using in vivo analyses and focusing on relevant cell types during pneumonic plague infection, we can identify host pathways that may be manipulated to extend the treatment window for pneumonic plague patients.Nikolas M. StasulliKara R. EichelbergerPaul A. PriceRoger D. PechousStephanie A. MontgomeryJoel S. ParkerWilliam E. GoldmanAmerican Society for MicrobiologyarticleMicrobiologyQR1-502ENmBio, Vol 6, Iss 5 (2015)
institution	DOAJ
collection	DOAJ
language	EN
topic	Microbiology QR1-502
spellingShingle	Microbiology QR1-502 Nikolas M. Stasulli Kara R. Eichelberger Paul A. Price Roger D. Pechous Stephanie A. Montgomery Joel S. Parker William E. Goldman Spatially Distinct Neutrophil Responses within the Inflammatory Lesions of Pneumonic Plague
description	ABSTRACT During pneumonic plague, the bacterium Yersinia pestis elicits the development of inflammatory lung lesions that continue to expand throughout infection. This lesion development and persistence are poorly understood. Here, we examine spatially distinct regions of lung lesions using laser capture microdissection and transcriptome sequencing (RNA-seq) analysis to identify transcriptional differences between lesion microenvironments. We show that cellular pathways involved in leukocyte migration and apoptosis are downregulated in the center of lung lesions compared to the periphery. Probing for the bacterial factor(s) important for the alteration in neutrophil survival, we show both in vitro and in vivo that Y. pestis increases neutrophil survival in a manner that is dependent on the type III secretion system effector YopM. This research explores the complexity of spatially distinct host-microbe interactions and emphasizes the importance of cell relevance in assays in order to fully understand Y. pestis virulence. IMPORTANCE Yersinia pestis is a high-priority pathogen and continues to cause outbreaks worldwide. The ability of Y. pestis to be transmitted via respiratory droplets and its history of weaponization has led to its classification as a select agent most likely to be used as a biological weapon. Unrestricted bacterial growth during the initial preinflammatory phase primes patients to be infectious once disease symptoms begin in the proinflammatory phase, and the rapid disease progression can lead to death before Y. pestis infection can be diagnosed and treated. Using in vivo analyses and focusing on relevant cell types during pneumonic plague infection, we can identify host pathways that may be manipulated to extend the treatment window for pneumonic plague patients.
format	article
author	Nikolas M. Stasulli Kara R. Eichelberger Paul A. Price Roger D. Pechous Stephanie A. Montgomery Joel S. Parker William E. Goldman
author_facet	Nikolas M. Stasulli Kara R. Eichelberger Paul A. Price Roger D. Pechous Stephanie A. Montgomery Joel S. Parker William E. Goldman
author_sort	Nikolas M. Stasulli
title	Spatially Distinct Neutrophil Responses within the Inflammatory Lesions of Pneumonic Plague
title_short	Spatially Distinct Neutrophil Responses within the Inflammatory Lesions of Pneumonic Plague
title_full	Spatially Distinct Neutrophil Responses within the Inflammatory Lesions of Pneumonic Plague
title_fullStr	Spatially Distinct Neutrophil Responses within the Inflammatory Lesions of Pneumonic Plague
title_full_unstemmed	Spatially Distinct Neutrophil Responses within the Inflammatory Lesions of Pneumonic Plague
title_sort	spatially distinct neutrophil responses within the inflammatory lesions of pneumonic plague
publisher	American Society for Microbiology
publishDate	2015
url	https://doaj.org/article/43c57dc31d544828a34444bf8f493d61
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Spatially Distinct Neutrophil Responses within the Inflammatory Lesions of Pneumonic Plague

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