Laboratoire d'Immunogénétique, Centre de Recherche du Centre Hospitalier de l'Université de Montréal (CRCHUM), Montréal, QC H2X 0A9, Canada.
Département de Microbiologie, Infectiologie et Immunologie de l'Université de Montréal, Montréal, QC H3C 3J7, Canada.
Viruses. 2018 Apr 23;10(4):215. doi: 10.3390/v10040215.
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.
非洲占全球人类免疫缺陷病毒 (HIV) 感染的大多数，其中大多数通过异性性行为影响女性。目前，HIV 尚无治愈方法，疫苗和杀微生物剂的开发仍然是消除大流行的最佳解决方案。我们和其他人已经在非洲女性性工作者 (CSW) 中确定了 HIV 高暴露阴性 (HESN) 个体。对 HESN 的生殖器样本的分析表明，存在强大的先天和抗炎条件、HIV 特异性 CD4⁺和 CD8⁺ T 细胞以及免疫球蛋白 (Igs)，以及增加的调节性细胞群体，所有这些都支持针对 HIV 入侵的强度和控制之间的微妙平衡。此外，我们最近表明，与未感染 HIV 的非 CSW 女性相比，HESN 血液中的先天边缘区 (MZ) B 细胞频率降低，表明它们被募集到外周部位。这与事实相符，即已知调节 MZ 池的 B 淋巴细胞刺激物 (BLyS/BAFF) 的水平在 HESN 的血液中明显低于 HIV 感染的进展者，而 HIV 感染的 CSW 和未感染 HIV 的非 CSW 女性。有趣的是，MZ B 细胞可以结合 HIV gp120 并产生特异性 IgG 和 IgA，并且具有 B 调节潜力的倾向，这可以帮助对抗 HIV 并维持 HESN 中的低炎症状态。HESN 个体提供了一个极好的机会，可以为保护性设备的开发确定重要线索，并且应该努力征求在其自然对 HIV 免疫的背景下观察到的免疫反应。
