title: 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 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.
  
  
  OBJECTIVE
  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.
authors.affiliation: Department of Microbiology and Immunology, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina, USA.
authors.forename: Nikolas M
authors.initials: NM
authors.lastname: Stasulli
authors.affiliation: Department of Microbiology and Immunology, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina, USA.
authors.forename: Kara R
authors.initials: KR
authors.lastname: Eichelberger
authors.affiliation: Department of Microbiology and Immunology, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina, USA.
authors.forename: Paul A
authors.initials: PA
authors.lastname: Price
authors.affiliation: Department of Microbiology and Immunology, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina, USA.
authors.forename: Roger D
authors.initials: RD
authors.lastname: Pechous
authors.affiliation: Department of Pathology and Laboratory Medicine, Lineberger Comprehensive Cancer Center, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina, USA.
authors.forename: Stephanie A
authors.initials: SA
authors.lastname: Montgomery
authors.affiliation: Department of Genetics, Lineberger Comprehensive Cancer Center, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina, USA.
authors.forename: Joel S
authors.initials: JS
authors.lastname: Parker
authors.affiliation: Department of Microbiology and Immunology, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina, USA goldman@med.unc.edu.
authors.forename: William E
authors.identifier: http://orcid.org/0000-0002-1551-6718
authors.initials: WE
authors.lastname: Goldman
mesh_terms: D000818:Animals; D017209:Apoptosis; D001425:Bacterial Outer Membrane Proteins / Q000378:metabolism; D002465:Cell Movement; D002470:Cell Survival; D002478:Cells, Cultured; D004195:Disease Models, Animal; D020869:Gene Expression Profiling; D006651:Histocytochemistry; D006801:Humans; D061346:Laser Capture Microdissection; D008168:Lung / Q000473:pathology*; D008810:Mice, Inbred C57BL; D008954:Models, Biological; D009504:Neutrophils / Q000276:immunology* / Q000502:physiology; D010930:Plague / Q000473:pathology*; D015010:Yersinia pestis / Q000276:immunology*
chemical_list: D001425:Bacterial Outer Membrane Proteins; C060772:yopM protein, Yersinia