Obesity has been associated with greater severity of influenza virus
infection and impaired host defense. Exercise may confer health benefits even when
weight loss is not achieved, but it has not been determined if regular exercise improves immune defense against influenza A virus (IAV) in the obese condition. In this study, diet-induced obese mice and lean control mice exercised for eight weeks followed by
influenza viral infection. Exercise reduced disease severity in both obese and non-obese mice, but the mechanisms differed. Exercise reversed the
obesity-associated delay in bronchoalveolar-lavage (BAL) cell infiltration, restored BAL
cytokine and
chemokine production, and increased ciliary beat frequency and IFNα-related gene expression. In non-obese mice, exercise treatment reduced lung viral load, increased Type-I-IFN-related gene expression early during
infection, but reduced BAL inflammatory
cytokines and
chemokines. In both obese and non-obese mice, exercise increased serum anti-influenza virus specific IgG2c antibody, increased CD8+ T cell percentage in BAL, and reduced TNFα by
influenza viral NP-
peptide-responding CD8+ T cells. Overall, the results suggest that exercise "restores" the immune response of obese mice to a phenotype similar to non-obese mice by improving the delay in immune activation. In contrast, in non-obese mice exercise treatment results in an early reduction in lung viral load and limited inflammatory response.