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An inherent T cell deficit in healthy males to C. neoformans infection may begin to explain the sex susceptibility in incidence of cryptococcosis.
Biology of Sex Differences ( IF 7.9 ) Pub Date : 2019-09-02 , DOI: 10.1186/s13293-019-0258-2
Tiffany E Guess 1 , Joseph Rosen 1 , Natalia Castro-Lopez 2, 3 , Floyd L Wormley 2, 3 , Erin E McClelland 1
Affiliation  

BACKGROUND Cryptococcus neoformans, the causative agent of cryptococcosis, causes ~ 181,000 deaths annually, with males having a higher incidence of disease than females (7M:3F). The reason for this sex bias remains unclear. We hypothesized that this disparity was due to biological differences between the male and female immune response. METHODS Peripheral blood mononuclear cells (PBMCs) from healthy donors were isolated and infected with C. neoformans ± exogenous testosterone or 17-β-estradiol. C. neoformans, B, T, and NK cell proliferation was quantified by flow cytometry. Cytokine analysis was conducted via protein array or ELISA. Serological testing was conducted to determine previous exposure to C. neoformans. RESULTS C. neoformans proliferated more in male PBMCs. T cell percentages in both sexes were lower in infected versus uninfected cells. Male PBMCs had lower CD3+, CD4+, and CD8+ T cells percentages during infection compared to females. Cytokine profiles showed differences in uninfected male and female PBMCs, which subsided during infection. Only one donor was sero-negative for prior C. neoformans exposure. There was an effect of estrogen in one dataset. CONCLUSIONS These results suggest that males show an inherent deficit in T cell response during infection, which may contribute to the increased incidence of disease in males.

中文翻译:

在健康男性中,固有的T细胞缺陷会感染新孢子虫,这可能开始解释隐球菌病发病率的性别敏感性。

背景技术新型隐球菌是隐球菌病的病原体,每年导致约181,000例死亡,其中男性的发病率高于女性(7M:3F)。这种性别偏见的原因尚不清楚。我们假设这种差异是由于男性和女性免疫反应之间的生物学差异引起的。方法分离健康捐献者的外周血单个核细胞(PBMC),并感染新孢子虫±外源性睾丸激素或17-β-雌二醇。通过流式细胞术定量新孢梭菌,B,T和NK细胞的增殖。通过蛋白质阵列或ELISA进行细胞因子分析。进行血清学测试以确定先前接触新孢子虫。结果新形成梭状芽胞杆菌在男性PBMC中增殖更多。感染和未感染的细胞中,男女的T细胞百分比均较低。与女性相比,男性PBMC在感染过程中具有较低的CD3 +,CD4 +和CD8 + T细胞百分比。细胞因子谱显示未感染的男性和女性PBMC的差异,在感染期间会逐渐消退。对于先前接触过的新福寿球菌,只有一名供者血清阴性。在一个数据集中有雌激素的作用。结论这些结果表明,男性在感染过程中表现出T细胞反应的固有缺陷,这可能导致男性疾病的发病率增加。在一个数据集中有雌激素的作用。结论这些结果表明,男性在感染过程中表现出T细胞反应的固有缺陷,这可能导致男性疾病的发病率增加。在一个数据集中有雌激素的作用。结论这些结果表明,男性在感染过程中表现出T细胞反应的固有缺陷,这可能导致男性疾病的发病率增加。
更新日期:2020-04-22
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