The Effects of Adiposity and Type II Diabetes on the Immune Response to Influenza Virus in Adults

Paich, Heather

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March 22, 2019

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Paich, Heather
- Affiliation: Gillings School of Global Public Health, Department of Nutrition

Abstract

There are very limited data on mechanisms that mediate the obesity-associated and type II diabetes-associated impairments in immune function against viral infections, such as with the influenza virus. The purpose of this dissertation was to assess the humoral and cellular immune responses to the influenza virus, as well as to examine the effects of type II diabetes on T cell metabolism. This dissertation followed three aims. Aim 1 utilized a convenience sample to determine the antibody response to influenza vaccination in healthy weight, overweight, and obese adults at one and 11 months post vaccination. Higher body mass index (BMI) was associated with a greater decline in antibody titers to influenza strains at eleven months post vaccination, suggesting that overweight and obese individuals may not be as protected throughout the duration of the flu season compared to healthy weight individuals. Aim 2 consisted of a series of several studies comparing the cellular immune response to influenza virus in dendritic cells, cluster of differentiation (CD) 4+ T cells, and CD8+ T cells from healthy weight, overweight, and obese adults following ex vivo stimulation with live influenza virus. Although markers of dendritic cell activation and function remained intact, markers of T cell activation and function were significantly impaired in overweight and obese, compared to healthy weight adults. Together these data suggest that there would be significant deficiencies in the activation and cytotoxic function of CD8+ T cells, as well as in the activation and helper function of CD4+ T cells resulting from overweight and obesity. Aim 3 was an exploratory aim designed to generate preliminary data towards answering the question of how obesity with or without type II diabetes will affect T cell glucose metabolism. The data suggests that there are differences in glucose metabolism in unstimulated T cells from obese individuals with and without type II diabetes. The results of this dissertation indicate that both overweight and obesity impair the humoral and cellular immune response to influenza virus and that type II diabetes may alter T cell metabolism.

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