Systems analysis of sex differences reveals an immunosuppressive role for testosterone in the response to influenza vaccination
Systems analysis of sex differences reveals an immunosuppressive role for testosterone in the response to influenza vaccination
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DOI：
10.1073/pnas.1321060111
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发表时间：
2014-01-14
影响因子：
11.1
通讯作者：
Davis, Mark M.
中科院分区：
文献类型：
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作者：
Furman, David;Hejblum, Boris P.;Davis, Mark M.
女性通常比男性有更强大的免疫反应，原因还不是很清楚。在这里，我们使用系统分析来研究这些差异，方法是分析53名不同年龄的女性和34名男性对三价季节性流感灭活疫苗(TIV)和大量免疫系统成分的中和抗体反应，包括血清细胞因子和趋化因子、血细胞亚群频率、全基因组基因表达以及对不同体外刺激的细胞反应。我们发现，与男性相比，女性无论年龄大小，对TIV的抗体反应和炎性细胞因子的表达都更高。这种炎症状态与单核细胞中磷酸化的STAT3蛋白水平有关，但与疫苗的血清学反应无关。相比之下，使用机器学习的方法，我们识别了一组与脂质生物合成有关的基因，以前证明这些基因受到睾酮的上调，这些基因与男性较差的病毒中和活动有关。此外，血清睾酮水平和相关基因特征升高的男性对TIV的抗体反应最低。这些结果表明，雄激素和涉及脂肪代谢的基因之间存在很强的关联，这表明这些基因可能是男性和女性免疫反应差异的重要驱动因素。
Females have generally more robust immune responses than males for reasons that are not well-understood. Here we used a systems analysis to investigate these differences by analyzing the neutralizing antibody response to a trivalent inactivated seasonal influenza vaccine (TIV) and a large number of immune system components, including serum cytokines and chemokines, blood cell subset frequencies, genome-wide gene expression, and cellular responses to diverse in vitro stimuli, in 53 females and 34 males of different ages. We found elevated antibody responses to TIV and expression of inflammatory cytokines in the serum of females compared with males regardless of age. This inflammatory profile correlated with the levels of phosphorylated STAT3 proteins in monocytes but not with the serological response to the vaccine. In contrast, using a machine learning approach, we identified a cluster of genes involved in lipid biosynthesis and previously shown to be up-regulated by testosterone that correlated with poor virus-neutralizing activity in men. Moreover, men with elevated serum testosterone levels and associated gene signatures exhibited the lowest antibody responses to TIV. These results demonstrate a strong association between androgens and genes involved in lipid metabolism, suggesting that these could be important drivers of the differences in immune responses between males and females.