Department of Microbiology and Immunology, Stanford University School of Medicine, Stanford, CA 94305-5323.
Proc Natl Acad Sci U S A. 2014 Jan 14;111(2):869-74. doi: 10.1073/pnas.1321060111. Epub 2013 Dec 23.
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.
女性的免疫反应通常比男性更强，但原因尚不清楚。在这里，我们通过系统分析，分析了对三价灭活季节性流感疫苗（TIV）和大量免疫系统成分（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）的中和抗体反应，研究了这些差异，该研究纳入了来自不同年龄的 53 名女性和 34 名男性。我们发现，无论年龄大小，与男性相比，女性对 TIV 的抗体反应和血清中炎症细胞因子的表达都更高。这种炎症表型与单核细胞中磷酸化 STAT3 蛋白的水平相关，但与疫苗的血清反应无关。相比之下，我们使用机器学习方法，鉴定出一组与脂质生物合成相关的基因，这些基因之前已被证实可被睾酮上调，与男性对病毒的中和活性差相关。此外，血清睾丸酮水平升高且相关基因特征的男性对 TIV 的抗体反应最低。这些结果表明雄激素和参与脂质代谢的基因之间存在很强的关联，表明这些可能是男性和女性免疫反应差异的重要驱动因素。
