Gender differences in innate responses and gene expression profiles in memory CD4 T cells are apparent very early during acute simian immunodeficiency virus infection
Gender differences in innate responses and gene expression profiles in memory CD4 T cells are apparent very early during acute simian immunodeficiency virus infection
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DOI：
10.1371/journal.pone.0221159
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发表时间：
2019-09-06
期刊：
影响因子：
3.7
通讯作者：
Mattapallil, Joseph J.
中科院分区：
文献类型：
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作者：
George, Jeffy;Johnson, Ryan C.;Mattapallil, Joseph J.
人类免疫缺陷病毒(HIV)疾病进展和共病的性别差异已被广泛报道。使用猴免疫缺陷病毒(SIV)感染恒河猴的模型，我们发现这些差异在感染过程中非常早期就很明显。虽然CD4T细胞或其亚群的比例没有发生重大变化，但在感染后第4天，雌性猕猴的中央记忆CD4T细胞被发现与雄性猕猴相比，对显著更多的基因进行了差异化调控。路径分析显示，经典路径和生物学路径都存在分歧，并持续到第10天。基因表达谱的改变伴随着血浆促炎症介质如MCP-1/CCL2、I-TAC/CXCL11和MIF水平的显著增加。虽然雌雄猕猴的血浆IFNA水平没有差异，但在出生后第10天，雌性猕猴淋巴组织中IFNA亚型14、16、干扰素β和干扰素omega的表达水平显著高于雄性猕猴。我们的结果表明，慢性感染过程中出现的致病后遗症可能是由于在HIV感染过程中很早就诱导的免疫反应的性别差异所形成的。
Gender differences in Human immunodeficiency virus (HIV) disease progression and comorbidities have been extensively reported. Using the simian immunodeficiency virus (SIV) infected rhesus macaque model, we show that these differences are apparent very early during the course of infection. Though there were no major changes in the proportions of CD4 T cells or its subsets, central memory CD4 T cells from female macaques were found to differentially regulate a significantly larger number of genes at day 4 post-infection (PI) as compared to males. Pathway analysis revealed divergence of both canonical and biological pathways that persisted at day 10 PI. Changes in gene expression profiles were accompanied by a significant increase in plasma levels of pro-inflammatory mediators such as MCP-1/CCL2, I-TAC/CXCL11, and MIF. Though plasma levels of IFNa did not differ between male and female macaques, the expression levels of IFNa subtype-14, 16, IFN beta, and IFN omega were significantly upregulated in the lymph nodes of female macaques at day 10 PI as compared to male macaques. Our results suggest that the pathogenic sequelae seen during chronic infection may be shaped by gender differences in immune responses induced very early during the course of HIV infection.