Abstract
Dendritic cells (DCs) are key immune sentinels linking the innate and adaptive immune systems. DCs recognise danger signals and initiate T-cell tolerance, memory and polarisation. They are critical cells in responding to a viral illness. Obese individuals have been shown to have an impaired response to vaccinations against virally mediated conditions and to have an increased susceptibility to multi-organ failure in response to viral illness. We investigated if DCs are altered in an obese cohort (mean body mass index 51.7±7.3 kg m−2), ultimately resulting in differential T-cell responses. Circulating DCs were found to be significantly decreased in the obese compared with the lean cohort (0.82% vs 2.53%). Following Toll-like receptor stimulation, compared with lean controls, DCs generated from the obese cohort upregulated significantly less CD83 (40% vs 17% mean fluorescence intensity), a molecule implicated in the elicitation of T-cell responses, particularly viral responses. Obese DCs produced twofold more of the immunosuppressive cytokine interleukin (IL)-10 than lean controls, and in turn stimulated fourfold more IL-4-production from allogenic naive T cells. We conclude that obesity negatively impacts the ability of DCs to mature and elicit appropriate T-cell responses to a general stimulus. This may contribute to the increased susceptibility to viral infection observed in severe obesity.
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Acknowledgements
AEH is supported by the National Children’s Research Centre. The Obesity Immunology Group is supported by Irish Health Research Board, NCRC and UCD Newman Fellowship Programme.
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O'Shea, D., Corrigan, M., Dunne, M. et al. Changes in human dendritic cell number and function in severe obesity may contribute to increased susceptibility to viral infection. Int J Obes 37, 1510–1513 (2013). https://doi.org/10.1038/ijo.2013.16
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DOI: https://doi.org/10.1038/ijo.2013.16
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