Premature birth : implications for early life immunity
department or school: Medicine, Faculty of
department or school: Medicine, Department of
data provider: DSpace
degree campus: UBCV
creator: Michalski, Christina
issued: 2023-01-31T08:00:00Z
issued: 2021
related degree: Doctor of Philosophy - PhD
degree grantor: University of British Columbia
description: Premature birth is a major contributor to under-five mortality, causing approximately 1 million deaths every year. This vulnerability stems from the high susceptibility of neonates, particularly those born prematurely, to severe life-threatening infections. The overarching goal of my thesis work was to study the immunological basis for preterm neonates’ vulnerability to infections. It was previously known that monocytes isolated from preterm cord blood show suppressed responses to innate immune activation. In Chapter 2, we employed untargeted transcriptomics comparing monocytes at rest and after LPS stimulation, from neonates born preterm (<33 weeks gestation), at term (>37 weeks gestation) and from adults. Results establish cellular energy metabolism as a major regulator of innate immune responsiveness during fetal life, perhaps to purposely limit overt inflammation in utero. Additionally, our experiments suggested a central role for mTORC1, and its negative regulator DDIT4L in suppressing innate immune responses in preterm monocytes. In Chapter 3, I developed a monocytic cell line model to study the impact of DDIT4L on innate immune function. DDIT4L overexpression limited protein synthesis, cellular proliferation and LPS-induced cytokine production. Additionally, experiments in primary neonatal monocytes revealed developmental changes in mitochondrial function. Lastly, data linking reduced DDIT4L expression to more severe inflammatory lung disease in preterm neonates point towards a putative role in preventing inflammatory-mediated tissue damage in neonates. Beyond the immediate postnatal period, preterm infants remain particularly vulnerable to respiratory viral infections. In Chapter 4, I studied infants at high-risk for respiratory syncytial virus (RSV) infections. I showed that most infants have been exposed to RSV, as evidenced by increased IgM titers, Fc receptor binding and antibody-mediated phagocytosis by the end of their first winter season. Overall, my …
aggregated CHO: https://circle.library.ubc.ca/rest/handle/2429/80608
note: PREMATURE BIRTH: IMPLICATIONS FOR EARLY LIFE IMMUNITY by Christina Michalski M.S., Rutgers University, 2015 B.Sc., Marburg University, 2014 A THESIS SUBMITTED IN PARTIAL FULFILLMENT OF THE REQUIREMENTS FOR THE DEGREE OF DOCTOR OF PHILOSOPHY in THE FACULTY OF GRADUATE AND POSTDOCTORAL STUDIES (Experimental Medicine) THE UNIVERSITY OF BRITISH COLUMBIA (Vancouver) December 2021 © Christina Michalski, 2021 ii The following individuals certify that they have read, and recommend to the Faculty of Graduate and Postdoctoral Studies for acceptance, the dissertation entitled: Premature Birth: Implications for Immunity in Early Life submitted by Christina Michalski in partial fulfillment of the requirements for the degree of Doctor of Philosophy in Experimental Medicine Examining Committee: Dr. Pascal Lavoie, Associate Professor, Department of Pediatrics, UBC Supervisor Dr. Laura Sly, Professor, Department of Pediatrics, UBC Supervisory Committee Member Dr. Fumio Takei, Professor, Department of Pathology & Laboratory Medicine, UBC University Examiner Dr. Helene Cote, Professor, Department of Pathology & Laboratory Medicine, UBC University Examiner Additional Supervisory Committee Members: Dr. Eric Jan, Professor, Department of Biochemistry & Molecular Biology, UBC Supervisory Committee Member Dr. Dan Luciani, Associate Professor, Department of Surgery, UBC Supervisory Committee Member iii Abstract Premature birth is a major contributor to under-five mortality, causing approximately 1 million deaths every year. This vulnerability stems from the high susceptibility of neonates, particularly those born prematurely, to severe life-threatening infections. The overarching goal of my thesis work was to study the immunological basis for preterm neonates’ vulnerability to infections. It was previously known that monocytes isolated from preterm cord blood show suppressed responses to innate immune activation. In Chapter 2, we employed untargeted transcriptomics comparing monocytes at re…
has type: Thesis/Dissertation
date issued: 2022-05
is shown at: 10.14288/1.0406208
language: eng
degree discipline: Experimental Medicine
provider: Vancouver : University of British Columbia Library
publisher: University of British Columbia
rights: Attribution-NonCommercial-NoDerivatives 4.0 International
rights URI: http://creativecommons.org/licenses/by-nc-nd/4.0/
scholar level: Graduate
contributor: Lavoie, Pascal M.
type: Text
identifier URI: http://hdl.handle.net/2429/80608