母婴垂直传播中 HIV-1 的性别特异性固有免疫选择与女性易感性增加有关。
Sex-specific innate immune selection of HIV-1 in utero is associated with increased female susceptibility to infection.
机构信息
Department of Paediatrics, University of Oxford, Oxford, UK.
HIV Pathogenesis Programme, The Doris Duke Medical Research Institute, University of KwaZulu-Natal, Durban, South Africa.
出版信息
Nat Commun. 2020 Apr 14;11(1):1767. doi: 10.1038/s41467-020-15632-y.
Female children and adults typically generate more efficacious immune responses to vaccines and infections than age-matched males, but also suffer greater immunopathology and autoimmune disease. We here describe, in a cohort of > 170 in utero HIV-infected infants from KwaZulu-Natal, South Africa, fetal immune sex differences resulting in a 1.5-2-fold increased female susceptibility to intrauterine HIV infection. Viruses transmitted to females have lower replicative capacity (p = 0.0005) and are more type I interferon-resistant (p = 0.007) than those transmitted to males. Cord blood cells from females of HIV-uninfected sex-discordant twins are more activated (p = 0.01) and more susceptible to HIV infection in vitro (p = 0.03). Sex differences in outcome include superior maintenance of aviraemia among males (p = 0.007) that is not explained by differential antiretroviral therapy adherence. These data demonstrate sex-specific innate immune selection of HIV associated with increased female susceptibility to in utero infection and enhanced functional cure potential among infected males.
女性儿童和成年人通常比同龄男性对疫苗和感染产生更有效的免疫反应，但也会遭受更大的免疫病理和自身免疫性疾病。我们在这里描述了来自南非夸祖鲁-纳塔尔省的 170 多名宫内 HIV 感染婴儿的队列，胎儿免疫性别差异导致女性对宫内 HIV 感染的易感性增加 1.5-2 倍。传播给女性的病毒复制能力较低（p=0.0005），对 I 型干扰素的抵抗力更强（p=0.007），而传播给男性的病毒则较弱。来自 HIV 未感染的性别不一致的双胞胎女性的脐带血细胞更活跃（p=0.01），并且更容易在体外感染 HIV（p=0.03）。结果的性别差异包括男性中更好地维持抗 HIV 血症（p=0.007），这不能用抗逆转录病毒治疗的差异来解释。这些数据表明，与 HIV 相关的先天免疫存在性别特异性选择，这与女性对宫内感染的易感性增加以及感染男性的功能性治愈潜力增强有关。
Zotero 插件