Obesity alters the immune response to influenza virus infection: a mechanism for immune modulation Public Deposited

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  • March 21, 2019
  • Smith, Alexia Genese
    • Affiliation: Gillings School of Global Public Health, Department of Nutrition
  • The incidence of obesity worldwide has reached epidemic proportions. This has had a significant economic and social impact due to the increase in co-morbidities associated with obesity (1). Obesity leads to changes in immune parameters under basal conditions (2), suggesting that obesity may result in impaired immune responses during an infection. Influenza virus infection is a leading cause of morbidity and mortality worldwide, and proper immune regulation is necessary for clearance of virus with minimal damage to the host. Given that obesity leads to impairment in immune function, we hypothesized that obesity would result in an impaired immune response following infection with influenza virus. Using a mouse model of diet-induced obesity, we found that influenza infected mice had minimal and delayed activation of the innate immune response, as well as a mortality rate that was eight times greater than normal weight mice. The lack of response was partially due to a reduction in mononuclear cell infiltration into the lungs during the early stages of infection. Obese mice also had impaired dendritic cell function, which is a critical link between the innate and cell-mediated immune responses, suggesting that cell-mediated responses during influenza infection were also affected by obesity. Indeed, obese mice had lower induction of cytokines that promote anti-viral T cell responses, impaired proliferation and cytokine production by T cells, and delayed infiltration of T cells to the infected lung. What was the cause of the immune dysfunction? Once possibility was the high circulating leptin levels found in obese mice. Leptin is a hormone that plays a role in both innate and cell-mediated immunity through phosphorylation of Signal transducer and activator of transcription 3 (STAT3) subsequent to binding to its receptor. Despite high circulating leptin, we found that obese mice had reduced STAT3 phosphorylation in immune cells during infection, indicating leptin signaling was impaired and may have mediated some of the immune changes that occurred in obese mice. When we analyzed the impact of direct leptin on immune cell function, we found that direct leptin signaling was not required for normal function. This was shown by correction of immune cell function when a functional neuro-specific leptin receptor was expressed in leptin receptor-deficient, db/db mice. Therefore, the impairment in immune responses that occur in obese mice is, in part, likely due to a lack of centrally mediated effects of leptin. Overall, this work implicates obesity as a risk factor for impaired immune responses during influenza virus infection and, furthermore, suggests that responses to other infections may be affected by obesity. Thus, the rapidly growing obese population in this country and other may at substantial risk for increased morbidity and mortality during the next influenza pandemic.
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  • In Copyright
  • Beck, Melinda A.
Degree granting institution
  • University of North Carolina at Chapel Hill
  • Open access

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