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dc.contributor.authorZerbib, Yoann
dc.contributor.authorJenkins, Emily K
dc.contributor.authorShojaei, Maryam
dc.contributor.authorMeyers, Adrienne F A
dc.contributor.authorHo, John
dc.contributor.authorBall, T Blake
dc.contributor.authorKeynan, Yoav
dc.contributor.authorPisipati, Amarnath
dc.contributor.authorKumar, Aseem
dc.contributor.authorKumar, Anand
dc.contributor.authorNalos, Marek
dc.contributor.authorTang, Benjamin M
dc.contributor.authorSchughart, Klaus
dc.contributor.authorMcLean, Anthony
dc.identifier.citationBMC Med Genomics. 2020 Feb 17;13(1):28. doi: 10.1186/s12920-020-0672-7.en_US
dc.description.abstractBACKGROUND: Influenza infections produce a spectrum of disease severity, ranging from a mild respiratory illness to respiratory failure and death. The host-response pathways associated with the progression to severe influenza disease are not well understood. METHODS: To gain insight into the disease mechanisms associated with progression to severe infection, we analyzed the leukocyte transcriptome in severe and moderate influenza patients and healthy control subjects. Pathway analysis on differentially expressed genes was performed using a topology-based pathway analysis tool that takes into account the interaction between multiple cellular pathways. The pathway profiles between moderate and severe influenza were then compared to delineate the biological mechanisms underpinning the progression from moderate to severe influenza. RESULTS: 107 patients (44 severe and 63 moderate influenza patients) and 52 healthy control subjects were included in the study. Severe influenza was associated with upregulation in several neutrophil-related pathways, including pathways involved in neutrophil differentiation, migration, degranulation and neutrophil extracellular trap (NET) formation. The degree of upregulation in neutrophil-related pathways were significantly higher in severely infected patients compared to moderately infected patients. Severe influenza was also associated with downregulation in immune response pathways, including pathways involved in antigen presentation such as CD4+ T-cell co-stimulation, CD8+ T cell and Natural Killer (NK) cells effector functions. Apoptosis pathways were also downregulated in severe influenza patients compare to moderate and healthy controls. CONCLUSIONS: These findings showed that there are changes in gene expression profile that may highlight distinct pathogenic mechanisms associated with progression from moderate to severe influenza infection.en_US
dc.rightsAttribution-NonCommercial-ShareAlike 4.0 International*
dc.subjectNeutrophil extracellular trapen_US
dc.titlePathway mapping of leukocyte transcriptome in influenza patients reveals distinct pathogenic mechanisms associated with progression to severe infection.en_US
dc.contributor.departmentHZI,Helmholtz-Zentrum für Infektionsforschung GmbH, Inhoffenstr. 7,38124 Braunschweig, Germany.en_US
dc.identifier.journalBMC Medical Genomicsen_US
dc.source.journaltitleBMC medical genomics

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Attribution-NonCommercial-ShareAlike 4.0 International
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