Diet-induced obesity in mice reduces the maintenance of influenza-specific CD8+ memory T cells

Abstract

Obesity has been associated with increasing the risk for type 2 diabetes and heart disease, but its influence on the immune response to viral infection is understudied. Memory T cells generated during a primary influenza infection are important for protection against subsequent influenza exposures. Previously, we have demonstrated that diet-induced obese (DIO) mice have increased morbidity and mortality following secondary influenza infection compared with lean mice. To determine whether the problem resided in a failure to maintain functional, influenza-specific CD8(+) memory T cells, male DIO and lean mice were infected with influenza X-31. At 84 d postinfection, DIO mice had a 10% reduction in memory T cell numbers. This reduction may have resulted from significantly reduced memory T cell expression of interleukin 2 receptor beta (IL-2R beta, CD122), but not IL-7 receptor alpha (CD127), which are both required for memory cell maintenance. Peripheral leptin resistance in the DIO mice may be a contributing factor to the impairment. Indeed, leptin receptor mRNA expression was significantly reduced in the lungs of obese mice, whereas suppressor of cytokine signaling (Socs)1 and Socs3 mRNA expression were increased. It is imperative to understand how the obese state alters memory T cells, because impairment in maintenance of functional memory responses has important implications for vaccine efficacy in an obese population.

FIGURE 1

Percentage (A,C) and number (B,D) of influenza-specific T_CM in lung (A,B) and spleen (C,D) of lean and obese mice at d 33 and 84 p.i. T_CM (CD8⁺/D^bNP_366–74⁺/CD44⁺/CD62L⁺) were identified using flow cytometry. Data are means + SEM, n = 6. Symbols indicate differences (P < 0.05): * vs. lean; § vs. d 33.

FIGURE 2

Percentage (A,B) and number (C) of influenza-specific CD8+ T_em in lungs of lean and obese mice at d 33 and 84 p.i. T_em (CD8⁺/D^bNP_366–74⁺/CD44⁺/CD62L⁻) were identified using flow cytometry. In B, data were obtained on d 84 p.i. Data are means + SEM, n = 6. Symbols indicate differences (P < 0.05): * vs. lean; § vs. d 33.

FIGURE 3

Percentage (A), count (B), and mean fluorescence intensity (C) of CD122 expression on influenza-specific T_em cells in lungs of lean and obese mice at d 33 and 84 p.i. CD122 expression on T_em cells (CD8⁺/D^bNP_366–74⁺/CD44⁺/CD62L⁻) was identified using flow cytometry. In B, data were obtained on d 33 p.i. Data are means + SEM, n = 6. Symbols indicate differences (P < 0.05): * vs. lean; § vs. d 33.