Influenza-Specific T Cell Memory: Influenza of Obesity, Weight Loss, Weight Gain
Public Deposited- Last Modified
- March 22, 2019
- Creator
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Rebeles, Jennifer
- Affiliation: Gillings School of Global Public Health, Department of Nutrition
- Abstract
- Obesity is a global epidemic, with 10% of men and 14% of women obese worldwide. Obesity is a known risk factor for increased complications and death from infection with influenza virus, and impairs the T cell response to both influenza infection and vaccination. As obesity is primarily a metabolic disorder, and immune cell function is dictated by metabolism of the immune cell, the effect of obesity on memory T cell metabolism following a secondary influenza infection was investigated. This dissertation addressed whether the metabolic environment at the time of memory T cell generation or at the time of re-challenge would influence T cell metabolism and function. C57BL/6J high fat diet-induced obese mice were infected with X-31 influenza virus to generate memory T cells, then switched to a low-fat diet to induce weight loss. Following weight loss and normalized fasting glucose levels, mice were re-infected with influenza Puerto Rico/8/34 (PR8) to activate the memory T cells in a newly generated lean state. Conversely, lean mice were infected with X-31 to generate memory T cells followed by a diet switch to a high fat diet to induce obesity. Following weight gain and elevated fasting glucose levels, mice were re-exposed to PR8. Compared with mice that were always lean, mice that were obese for both primary and secondary influenza infections had impaired T cell metabolism and function. Mice that lost weight maintained a metabolic phenotype that paralleled the always obese metabolic phenotype along with dysregulated frequencies of central memory, effector memory, and tissue resident memory T cell populations and decreased function of influenza-specific memory T cell subsets. Mice that had gained weight, and were previously lean, maintained a metabolic profile similar to the mice that were always lean, although also had T cell subset alterations and diminished function. Altogether, this data demonstrates that metabolic environment present at the time of memory T cell generation and at time of secondary immune challenge both impact T cell function. For the first time, obesity has been shown to alter T cell metabolism, and we demonstrate that weight loss will not restore T cell metabolism or function.
- Date of publication
- August 2017
- Keyword
- DOI
- Resource type
- Rights statement
- In Copyright
- Advisor
- Whitmire, Jason
- Coleman, Rosalind
- Makowski, Liza
- Hursting, Stephen
- Beck, Melinda A.
- Degree
- Doctor of Philosophy
- Degree granting institution
- University of North Carolina at Chapel Hill
- Graduation year
- 2017
- Language
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This work has no parents.
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