Year: 2022
Type: dissertation
Abstract: Severe malnutrition is associated with life-threatening complications and underlies morbidity and mortality in children under five. Immune dysregulations, especially of innate immunity, underlies these adverse outcomes. I used a lipopolysaccharide (LPS)-challenged protein restriction mouse model to investigate the impact of malnutrition and acute inflammation on neutrophil biology, the first responders of innate immunity that remain understudied in malnutrition. Following LPS, the malnourished mice were more susceptible to disease and mortality. Neutrophils (Ly6G+ cells) were expanded in the lungs of malnourished mice. However, neutrophil-mediated ROS production was reduced. Gene expression of transcription factors was also reduced in the bone marrow of these mice. These transcription factors control the gain of neutrophil effector functions throughout development. Therefore, this evidence points to changes in the neutrophil-intrinsic program driving increased susceptibility of the malnourished mice to mortality following acute inflammation. Overall, this study provides a novel understanding of neutrophil responses in malnutrition and inflammation.
Source: TSpace (University of Toronto)
Author: Thind, Mehakpreet Kaur
Institution: University of Toronto
Language: English
Subfield: Immunology
Field: Immunology and Microbiology
Domain: Life Sciences
Open Access status: green
OpenAlex ID: W7132877030