LPS-induced interferon response networks predict severe lower respiratory infection susceptibility in the first year of life

James Read

doi:10.26182/1654-7g62

LPS-induced interferon response networks predict severe lower respiratory infection susceptibility in the first year of life

James Read

UWA Medical School

Research output: Thesis › Doctoral Thesis

48 Downloads (Pure)

Abstract

Severe lower respiratory infections (sLRIs) are a leading cause of infant hospitalisation, and a major risk factor of asthma development. Employing systems biology approaches, this thesis demonstrates that interferon-signaling networks induced at birth by bacterial lipopolysaccharide (LPS), and not viral-related stimuli, can predict sLRIs in infancy. Further, LPS-induced interferon responses exhibited strong developmental regulation between birth and 5 years. This suggests that early life innate immune responses to bacterial products play a major role in sLRI susceptibility and subsequent asthma development. Accordingly, early-life LPS-induced response patterns represent a novel predictor of at-risk infants and a logical target for drug development.

Original language	English
Qualification	Doctor of Philosophy
Awarding Institution	The University of Western Australia
Supervisors/Advisors	Bosco, Anthony, Supervisor Strickland, Deborah, Supervisor Holt, Patrick, Supervisor Reinke, Stacey N., Supervisor, External person Kicic, Anthony, Supervisor Martino, David, Supervisor Whitehouse, Andrew, Supervisor
Thesis sponsors	Australian Government Research Training Program
Award date	25 Jan 2023
DOIs	https://doi.org/10.26182/1654-7g62
Publication status	Unpublished - 2023

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10.26182/1654-7g62

THESIS - DOCTOR OF PHILOSOPHY - READ James -2023
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5 Article
1 Review article

Lipopolysaccharide-induced interferon response networks at birth are predictive of severe viral lower respiratory infections in the first year of life
Read, J. F., Serralha, M., Mok, D., Holt, BJ., Cruickshank, M., Karpievitch, Y. V., Broadhurst, D. I., Sly, P. D., Strickland, D. H., Reinke, S. N., Holt, P. G. & Bosco, A., 5 Aug 2022, In: Frontiers in Immunology. 13, 876654.
Research output: Contribution to journal › Article › peer-review

Open Access
2 Citations (Scopus)
Decoding susceptibility to respiratory viral infections and asthma inception in children
Read, J. F. & Bosco, A., 1 Sept 2020, In: International Journal of Molecular Sciences. 21, 17, p. 1-19 19 p., 6372.
Research output: Contribution to journal › Review article › peer-review

Open Access
10 Citations (Web of Science)
Immunoinflammatory responses to febrile lower respiratory infections in infants display uniquely complex/intense transcriptomic profiles
Jones, A. C., Anderson, D., Galbraith, S., Fantino, E., Cardenas, D. G., Read, J. F., Serralha, M., Holt, B. J., Strickland, D. H., Sly, P. D., Bosco, A. & Holt, P. G., Nov 2019, In: Journal of Allergy and Clinical Immunology. 144, 5, p. 1411-1413 3 p.
Research output: Contribution to journal › Article › peer-review

3 Citations (Scopus)

Cite this

@phdthesis{39682fefb21f42618ac3764e1b869b2d,

title = "LPS-induced interferon response networks predict severe lower respiratory infection susceptibility in the first year of life",

abstract = "Severe lower respiratory infections (sLRIs) are a leading cause of infant hospitalisation, and a major risk factor of asthma development. Employing systems biology approaches, this thesis demonstrates that interferon-signaling networks induced at birth by bacterial lipopolysaccharide (LPS), and not viral-related stimuli, can predict sLRIs in infancy. Further, LPS-induced interferon responses exhibited strong developmental regulation between birth and 5 years. This suggests that early life innate immune responses to bacterial products play a major role in sLRI susceptibility and subsequent asthma development. Accordingly, early-life LPS-induced response patterns represent a novel predictor of at-risk infants and a logical target for drug development.",

keywords = "Innate immunity, Systems biology, Interferon, Multiomics, Transcriptomics, Immunology, Respiratory infection, Lipopolysaccharide",

author = "James Read",

year = "2023",

doi = "10.26182/1654-7g62",

language = "English",

school = "The University of Western Australia",

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T1 - LPS-induced interferon response networks predict severe lower respiratory infection susceptibility in the first year of life

AU - Read, James

PY - 2023

Y1 - 2023

N2 - Severe lower respiratory infections (sLRIs) are a leading cause of infant hospitalisation, and a major risk factor of asthma development. Employing systems biology approaches, this thesis demonstrates that interferon-signaling networks induced at birth by bacterial lipopolysaccharide (LPS), and not viral-related stimuli, can predict sLRIs in infancy. Further, LPS-induced interferon responses exhibited strong developmental regulation between birth and 5 years. This suggests that early life innate immune responses to bacterial products play a major role in sLRI susceptibility and subsequent asthma development. Accordingly, early-life LPS-induced response patterns represent a novel predictor of at-risk infants and a logical target for drug development.

AB - Severe lower respiratory infections (sLRIs) are a leading cause of infant hospitalisation, and a major risk factor of asthma development. Employing systems biology approaches, this thesis demonstrates that interferon-signaling networks induced at birth by bacterial lipopolysaccharide (LPS), and not viral-related stimuli, can predict sLRIs in infancy. Further, LPS-induced interferon responses exhibited strong developmental regulation between birth and 5 years. This suggests that early life innate immune responses to bacterial products play a major role in sLRI susceptibility and subsequent asthma development. Accordingly, early-life LPS-induced response patterns represent a novel predictor of at-risk infants and a logical target for drug development.

KW - Innate immunity

KW - Systems biology

KW - Interferon

KW - Multiomics

KW - Transcriptomics

KW - Immunology

KW - Respiratory infection

KW - Lipopolysaccharide

U2 - 10.26182/1654-7g62

DO - 10.26182/1654-7g62

M3 - Doctoral Thesis

ER -

LPS-induced interferon response networks predict severe lower respiratory infection susceptibility in the first year of life

Abstract

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Research output

Lipopolysaccharide-induced interferon response networks at birth are predictive of severe viral lower respiratory infections in the first year of life

Decoding susceptibility to respiratory viral infections and asthma inception in children

Immunoinflammatory responses to febrile lower respiratory infections in infants display uniquely complex/intense transcriptomic profiles

Cite this