Diet‐induced obese mice exhibit heightened lung inflammatory and cross‐reactive CD8 T cell responses during a secondary 2009 pandemic H1N1 influenza infection

Obese individuals were at greater risk for hospitalization and death following infection with the 2009 pandemic H1N1 influenza virus (pH1N1). Although cross‐reactive memory T cells can limit pH1N1 death and disease severity, we have previously shown obese mice and humans exhibit impaired memory T cell function. To determine if obesity results in greater pH1N1 morbidity as a consequence of impaired cross‐reactive T cell defenses, diet‐induced obese and lean, control mice were infected with a sublethal dose of influenza PR8. After 5 wk, the mice were challenged with a lethal dose of heterologous pH1N1. Despite a lack of differences in mortality, obese mice lost more weight and exhibited greater lung viral burden, immune cell infiltration, pathology and reduced lung integrity during the secondary challenge. Consistent with the elevated lung inflammatory responses, obese mice had a greater number of cytotoxic effector memory CD8 + T cells in the lungs. To investigate a potential mechanism for the excess inflammatory and pathological responses in the lungs of obese mice, we assessed the distribution of anti‐inflammatory regulatory T cells (Tregs). Although obese mice had twice has many lung Tregs compared with lean mice, Tregs isolated from obese were 40% less functional. Taken together, drastic impairments in Treg function may contribute to excessive inflammation and greater pH1N1 infection severity in the obese. Grant Funding Source : NORK DK56350