Metabolic and functional impairment of CD8+ T cells from the lungs of influenza-infected obese mice

Background: Obesity increases influenza disease risk in millions of adults worldwide. In this study, we investigated the effect of diet-induced obesity on pulmonary CD8+ T cell metabolism and function as a mechanism of impairment. Methods: Male C57BL/6J mice were fed either control (10% kcal/g) or high-fat (60% kcal/g) diet. Sub-lethal A/PR/8/34 influenza virus infection generated a robust pulmonary immune response. T cell metabolism and function were assessed at day 10 and day 24 post infection. Results: At day 10 post infection, CD8+ T cells from obese mice had impaired oxidative and glycolytic metabolism, greater fatty acid uptake, and decreased effector populations and cytokine production. At infection resolution, obese mice had lower numbers of naive and central memory CD8+ T cell populations in the lungs. Conclusion: Diet-induced obesity increases influenza virus pathogenesis through CD8+ T cell mediated metabolic reprogramming resulting in suppressed effector CD8+ T cell function.