Unknown,Transcriptomics,Genomics,Proteomics

Dataset Information

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 is poorly understood. Here, we examine spatially distinct regions of lung lesions using laser capture microdissection and RNAseq analysis to identify transcriptional differences between lesion microenvironments. We show that cellular pathways involved in leukocyte migration and apoptosis are down regulated 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. We examine spatially distinct regions of lung lesions using laser capture microdissection and RNAseq analysis to identify transcriptional differences between lesion microenvironments. Sample types: uninfected BM-PMN, infected BM-PMN, lesion periphery, lesion center.

ORGANISM(S): Mus musculus

SUBMITTER: William Goldman

PROVIDER: E-GEOD-70819 | biostudies-arrayexpress |

REPOSITORIES: biostudies-arrayexpress

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Spatially distinct neutrophil responses within the inflammatory lesions of pneumonic plague.

Stasulli Nikolas M NM Eichelberger Kara R KR Price Paul A PA Pechous Roger D RD Montgomery Stephanie A SA Parker Joel S JS Goldman William E WE

mBio 20151013 5

<h4>Unlabelled</h4>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 leu ...[more]

PMID: 26463167

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Project description:Background: Mesenchymal stromal cells (MSC) have been proposed as a future cell based therapy for lung diseases like bronchiolitis obliterans syndrome (BOS). Theoretically, it might be beneficial to use lung resident MSC already adapted to the pulmonary environment. We therefore aimed to compare lung MSC with the well-characterized bone marrow MSC. Furthermore, MSC isolated from lung-transplanted patients with BOS were compared to MSC isolated from good outcome recipients. Methods: MSC were isolated from bone marrow (BM) and adult/fetal lung tissues and compared by a comprehensive panel of assays. Results:The gene expression profiles of adult lung derived and fetal lung derived MSC were very similar compared to BM derived MSC, with only 235 and 338 genes, respectively, being significantly differently expressed. Out of the 235 genes that were significantly different between adult lung derived and BM derived MSC, 90 genes were higher expressed in the lung derived MSC. In case of fetal lung derived MSC, 166 genes were higher expressed compared to the BM derived MSC. Interestingly, only, 89 genes were found to be expressed differently when comparing BM derived MSC to both, fetal and adult lung derived MSC, indicating that these genes are lung specific. Next, we went on to evaluate if MSC isolated from biopsies of lung-transplanted patients with BOS differed compared to patients without BOS, i.e. good outcome recipients. Here we found that four genes (Sox9, FAR2, LOC728855 and NDUFS5) were significantly higher expressed in MSC isolated from BOS patients Conclusions: This data demonstrates that lung resident MSC possess lung specific properties that should be taken into considerations when using MSC for cell-based therapy in severe lung disorders like BOS. These results also show that MSC isolated from lung-transplanted patients with BOS do not have an altered phenotype. Comparison of gene expression of MSC isolated from bone marrow, adult lung and fetal lung.

Dataset Information

Spatially distinct neutrophil responses within the inflammatory lesions of pneumonic plague

Publications

Spatially distinct neutrophil responses within the inflammatory lesions of pneumonic plague.

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