dc.contributor.authorFransiskus Xaverius Ivan
dc.date.accessioned2014-05-29T03:27:08Z
dc.date.accessioned2017-07-23T08:44:55Z
dc.date.available2014-05-29T03:27:08Z
dc.date.available2017-07-23T08:44:55Z
dc.date.copyright2013en_US
dc.date.issued2013
dc.identifier.citationFransiskus Xaverius Ivan. (2013). Systems-level host responses to highly and less virulent influenza A (H3N2) virus infections. Doctoral thesis, Nanyang Technological University, Singapore.
dc.identifier.urihttp://hdl.handle.net/10356/60639
dc.description.abstractSevere influenza infections have been associated with dysregulated innate immunity that involves macrophages and neutrophils. While the contributions of macrophages to the dysregulation have been broadly investigated, the contributions of neutrophils remain unclear. Hence, in this thesis, we uncovered systems-level neutrophil response to highly virulent influenza infection by employing MPRO neutrophils and highly virulent, mouse adapted H3N2 influenza virus (HVI). Firstly, we showed that HVI induced hypercytokinemia and increased antiviral (interferon) response in the infected lungs. Moreover, increased apoptotic activity and under-expression of genes associated with metabolic and developmental processes mirrored severe pathological changes in HVI-infected lungs. Following pathway analysis, we highlighted the significant roles of the TREM1 signaling pathway in enhancing cytokine expression, and linked the hypercytokinemia to metabolic defect through the activation of LPS/IL1-mediated inhibition of retinoid X receptor (RXR) function pathway. With regards to infection of MPRO neutrophils (optimally containing 20%-30% mature neutrophils, as inspected with differential counting of giemsa-stained cells and flow cytometry based on neutrophil markers), influenza virus could induce apoptosis even though its infection was abortive. Finally, we revealed that HVI mainly activated a rapid induction of type I interferon-inducible genes in MPRO neutrophils, an event that potentially contributes to the dysregulated innate immunity observed in vivo.en_US
dc.format.extent212 p.en_US
dc.language.isoenen_US
dc.subjectDRNTU::Engineering::Computer science and engineeringen_US
dc.titleSystems-level host responses to highly and less virulent influenza A (H3N2) virus infectionsen_US
dc.typeThesis
dc.contributor.supervisor2Zheng Jieen_US
dc.contributor.researchSingapore-MIT Alliance Programmeen_US
dc.contributor.schoolSchool of Computer Engineeringen_US
dc.contributor.supervisorRajapakse Jagath Chandanaen_US
dc.description.degreeDOCTOR OF PHILOSOPHY (SCE)en_US
dc.identifier.doihttps://doi.org/10.32657/10356/60639


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