Obesity-Induced Changes in T-Cell Metabolism Are Associated With Impaired Memory T-Cell Response to Influenza and Are Not Reversed With Weight Loss

作者：Jennifer Rebeles, William D. Green, Yazan Alwarawrah, Amanda Nichols, William Eisner, Keiko Danzaki, Nancie J. MacIver, Melinda A. Beck · 发表于：The Journal of Infectious Diseases · 年份：2018 · DOI：10.1093/infdis/jiy700 · 被引用次数：78 · 研究领域：Diabetes and associated disorders、Adipokines, Inflammation, and Metabolic Diseases、Influenza Virus Research Studies

BACKGROUND: Obesity is an independent risk factor for increased influenza mortality and is associated with impaired memory T-cell response, resulting in increased risk of infection. In this study, we investigated if weight loss would restore memory T-cell response to influenza. METHODS: Male C57BL/6J mice were fed either low-fat or high-fat diet to induce obesity. Once obesity was established, all mice received primary infection with influenza X-31. Following a recovery period, we switched half of the obese group to a low-fat diet to induce weight loss. Fifteen weeks after diet switch, all mice were given a secondary infection with influenza PR8, and memory T-cell function and T-cell metabolism were measured. RESULTS: Following secondary influenza infection, memory T-cell subsets in the lungs of obese mice were decreased compared to lean mice. At the same time, T cells from obese mice were found to have altered cellular metabolism, largely characterized by an increase in oxygen consumption. Neither impaired memory T-cell response nor altered T-cell metabolism was reversed with weight loss. CONCLUSION: Obesity-associated changes in T-cell metabolism are associated with impaired T-cell response to influenza, and are not reversed with weight loss.