Natural Immunity to HIV: A Template for Vaccine Strategies.
Natural Immunity to HIV: A Template for Vaccine Strategies.
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DOI：
10.3390/v10040215
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发表时间：
2018-04-23
期刊：
影响因子：
--
通讯作者：
Roger M
中科院分区：
文献类型：
--
作者：
Fourcade L;Poudrier J;Roger M
非洲占全球人体免疫机能丧失病毒（艾滋病毒）感染的大多数，其中大多数通过异性性交感染妇女。目前，艾滋病毒无法治愈，研制疫苗和杀微生物剂仍然是根除这一流行病的最佳解决办法。我们和其他人在非洲女性商业性工作者（CSW）中发现了HIV高度暴露血清阴性（HESN）个体。对来自HESN的生殖器样本的分析已经证明了有效的先天性和抗炎性条件，HIV特异性CD 4+和CD 8 + T细胞以及免疫球蛋白（Ig），以及增加的调节细胞群，所有这些都支持强度和对HIV入侵的控制之间的微妙平衡。此外，我们最近表明，先天边缘区（MZ）B细胞的频率降低，在血液中的HESN相比，艾滋病毒未感染的非CSW妇女，这表明他们的招聘到周边网站。这与以下事实相一致：与HIV感染的CSW和HIV未感染的非CSW妇女相比，HESN血液中的B淋巴细胞刺激因子（BLyS/BAFF）水平显著较低，已知其形成MZ池，其过表达导致HIV感染的进展者中MZ失调。有趣的是，MZ B细胞可以结合HIV gp 120并产生特异性IgG和伊加，并且具有B调节潜力的倾向，这可能有助于对抗HIV和维持HESN中的低炎症状况。HESN个体提供了一个特殊的机会，以确定重要的线索，为保护装置的发展，努力的目的是征求免疫反应的情况下，他们的自然免疫艾滋病毒。
Africa accounts for the majority of global human immunodeficiency virus (HIV) infections, most of which affect women through heterosexual intercourse. Currently, there is no cure for HIV and the development of vaccines and microbicides remains the best solution to eradicate the pandemic. We and others have identified HIV highly-exposed seronegative (HESN) individuals among African female commercial sex workers (CSWs). Analyses of genital samples from HESNs have demonstrated potent innate and anti-inflammatory conditions, HIV-specific CD4+ and CD8+ T-cells as well as immunoglobulins (Igs), and increased regulatory cell populations, all of which support a delicate balance between strength and control against HIV intrusion. Moreover, we have recently shown that frequencies of innate marginal zone (MZ) B-cells are decreased in the blood of HESNs when compared to HIV-uninfected non-CSW women, suggesting their recruitment to peripheral sites. This coincides with the fact that levels of B lymphocyte stimulator (BLyS/BAFF), known to shape the MZ pool and whose overexpression leads to MZ deregulation in HIV-infected progressors, are significantly lower in the blood of HESNs when compared to both HIV-infected CSWs and HIV-uninfected non-CSW women. Interestingly, MZ B-cells can bind HIV gp120 and produce specific IgG and IgA, and have a propensity for B regulatory potential, which could help both the fight against HIV and maintenance of low inflammatory conditions in HESNs. HESN individuals provide an exceptional opportunity to identify important clues for the development of protective devices, and efforts should aim at soliciting immune responses observed in the context of their natural immunity to HIV.
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