Ploquin Mickaël J, Silvestri Guido, Müller-Trutwin Michaela
aInstitut Pasteur, Unité HIV, Inflammation and Persistence, Paris, France bDivision of Immunology and Microbiology, Yerkes National Primate Research Center, Atlanta, Georgia, USA.
Curr Opin HIV AIDS. 2016 Mar;11(2):201-8. doi: 10.1097/COH.0000000000000238.
The review summarizes studies in natural hosts, with a particular focus on the control of immune activation and new insights into viral reservoirs. We discuss why these findings are relevant for HIV research today.
AIDS resistance in natural hosts is characterized by a rapid control of inflammatory processes in response to simian immunodeficiency virus infection despite persistent viremia. Although CD4 T cells are dramatically depleted in the intestine in primary infection, interleukin 17-producing T helper cells (Th17) are preserved and natural hosts lack microbial translocation. Thus, viral replication in the gut is not sufficient to explain mucosal damage, but additional factors are necessary. Natural hosts also display a lower infection rate of stem-cell memory, central memory and follicular helper T cells. The follicles are characterized by a lack of viral trapping and the viral replication in secondary lymphoid organs is rapidly controlled. Hence, the healthy status of natural hosts is associated with preserved lymphoid environments.
Understanding the underlying mechanisms of preservation of Th17 and of the low contribution of stem-cell memory, central memory and follicular helper T cells to viral reservoirs could benefit the search for preventive and curative approaches of HIV. Altogether, the complementarity of the model helps to identify strategies aiming at restoring full capacity of the immune system and decreasing the size of the viral reservoirs.
本综述总结了在天然宿主中的研究，特别关注免疫激活的控制以及病毒储存库的新见解。我们讨论了为什么这些发现与当今的HIV研究相关。
天然宿主中的艾滋病抗性表现为尽管存在持续病毒血症，但在感染猿猴免疫缺陷病毒后能迅速控制炎症过程。虽然在初次感染时肠道中的CD4 T细胞会显著减少，但产生白细胞介素17的辅助性T细胞（Th17）得以保留，且天然宿主不存在微生物易位。因此，肠道中的病毒复制不足以解释黏膜损伤，还需要其他因素。天然宿主中干细胞记忆性T细胞、中枢记忆性T细胞和滤泡辅助性T细胞的感染率也较低。滤泡的特点是缺乏病毒捕获，且次级淋巴器官中的病毒复制能迅速得到控制。因此，天然宿主的健康状态与保留的淋巴环境相关。
了解Th17得以保留以及干细胞记忆性T细胞、中枢记忆性T细胞和滤泡辅助性T细胞对病毒储存库贡献较低的潜在机制，可能有助于寻找HIV的预防和治疗方法。总之，该模型的互补性有助于确定旨在恢复免疫系统全部功能并减小病毒储存库规模的策略。
