Changes in human dendritic cell number and function in severe obesity may contribute to increased susceptibility to viral infection
Changes in human dendritic cell number and function in severe obesity may contribute to increased susceptibility to viral infection
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DOI：
10.1038/ijo.2013.16
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发表时间：
2013-11-01
影响因子：
4.9
通讯作者：
Hogan, A. E.
中科院分区：
文献类型：
--
作者：
O'Shea, D.;Corrigan, M.;Hogan, A. E.
树突状细胞 (DC) 是连接先天免疫系统和适应性免疫系统的关键免疫哨兵。 DC 识别危险信号并启动 T 细胞耐受、记忆和极化。它们是应对病毒性疾病的关键细胞。肥胖个体已被证明对针对病毒介导疾病的疫苗接种反应受损，并且对病毒性疾病引起的多器官衰竭的易感性增加。我们研究了肥胖人群（平均体重指数 51.7 +/- 7.3 kgm(-2)）中 DC 是否发生改变，最终导致 T 细胞反应差异。与瘦人相比，肥胖者的循环 DC 显着减少（0.82% vs 2.53%）。在 Toll 样受体刺激后，与瘦对照相比，肥胖组产生的 DC 上调的 CD83 显着减少（平均荧光强度为 40% 对 17%），CD83 是一种与引发 T 细胞反应，特别是病毒反应有关的分子。肥胖 DC 产生的免疫抑制性细胞因子白细胞介素 (IL)-10 是瘦对照的两倍，反过来又刺激同种异体初始 T 细胞产生四倍多的 IL-4。我们得出的结论是，肥胖会对 DC 成熟和引发适当 T 细胞对一般刺激做出反应的能力产生负面影响。这可能导致严重肥胖者对病毒感染的易感性增加。
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 kgm(-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.