Systems-level host responses to highly and less virulent influenza A (H3N2) virus infections

Severe 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 uncover...

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Main Author: Fransiskus Xaverius Ivan
Other Authors: Rajapakse Jagath Chandana
Format: Theses and Dissertations
Language:English
Published: 2014
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Online Access:https://hdl.handle.net/10356/60639
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Institution: Nanyang Technological University
Language: English
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spelling sg-ntu-dr.10356-606392020-11-11T02:27:54Z Systems-level host responses to highly and less virulent influenza A (H3N2) virus infections Fransiskus Xaverius Ivan Rajapakse Jagath Chandana Singapore-MIT Alliance Programme Zheng Jie DRNTU::Engineering::Computer science and engineering Severe 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. DOCTOR OF PHILOSOPHY (CSB) 2014-05-29T03:27:08Z 2014-05-29T03:27:08Z 2013 2013 Thesis Fransiskus Xaverius Ivan. (2013). Systems-level host responses to highly and less virulent influenza A (H3N2) virus infections. Doctoral thesis, Nanyang Technological University, Singapore. https://hdl.handle.net/10356/60639 10.32657/10356/60639 en 212 p. application/pdf
institution Nanyang Technological University
building NTU Library
continent Asia
country Singapore
Singapore
content_provider NTU Library
collection DR-NTU
language English
topic DRNTU::Engineering::Computer science and engineering
spellingShingle DRNTU::Engineering::Computer science and engineering
Fransiskus Xaverius Ivan
Systems-level host responses to highly and less virulent influenza A (H3N2) virus infections
description Severe 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.
author2 Rajapakse Jagath Chandana
author_facet Rajapakse Jagath Chandana
Fransiskus Xaverius Ivan
format Theses and Dissertations
author Fransiskus Xaverius Ivan
author_sort Fransiskus Xaverius Ivan
title Systems-level host responses to highly and less virulent influenza A (H3N2) virus infections
title_short Systems-level host responses to highly and less virulent influenza A (H3N2) virus infections
title_full Systems-level host responses to highly and less virulent influenza A (H3N2) virus infections
title_fullStr Systems-level host responses to highly and less virulent influenza A (H3N2) virus infections
title_full_unstemmed Systems-level host responses to highly and less virulent influenza A (H3N2) virus infections
title_sort systems-level host responses to highly and less virulent influenza a (h3n2) virus infections
publishDate 2014
url https://hdl.handle.net/10356/60639
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