Naranjo-Covo María M, Rincón-Tabares Daniel S, Flórez-Álvarez Lizdany, Hernandez Juan C, Zapata-Builes Wildeman
Grupo Inmunovirología, Facultad de Medicina, Universidad de Antioquia, Medellín, Colombia.
Grupo Infettare, Facultad de Medicina, Universidad Cooperativa de Colombia, Medellín, Colombia.
Immun Inflamm Dis. 2025 Feb;13(2):e70138. doi: 10.1002/iid3.70138.
Although repeated exposure to HIV-1 can result in infection, some individuals remain seronegative without clinical or serologic evidence of infection; these individuals are known as HIV-1-exposed seronegative individuals. This population has been extensively studied to understand the mechanisms associated with natural resistance to HIV infection. Two main hypotheses have been proposed to explain this resistance: some researchers associated resistance with a low activation phenotype characterized by a decrease in the activation and proliferation of immune system cells linked with infection control and decreased production of cytokines and pro-inflammatory molecules, whereas others suggest that resistance is related to immune system activation and the expression of high levels of chemokines, pro-inflammatory cytokines and antiviral molecules.
Our study aims to review and analyze the most relevant evidence supporting the role of the activation level of the immune system during natural resistance to HIV-1 infection.
A search was conducted via the PubMed, SciELO and ScienceDirect databases. The literature search was performed in a nonsystematic manner. Articles published in the last five decades addressing immune activation mechanisms in natural resistance to HIV were reviewed.
A low-activation phenotype, characterized by a high frequency of Treg cells; reduced expression of CD25, CD38, and HLA-DR; and lower production of pro-inflammatory cytokines in peripheral and mucosal tissues, plays a key role in reducing the number of activated cells susceptible to infection, but it minimizes chronic inflammation, facilitating viral entry and spread. In contrast, the activation phenotype is associated with high expression of markers such as CD25, CD38, and HLA-DR, along with elevated high levels of interferon-stimulated genes and pro-inflammatory cytokines. This profile could promote infection control while increasing the number of virus-susceptible cells.
The complexity of the immune response during HIV exposure, reflected in the conflicting evidence concerning whether low or high immune activation offers protection against infection, suggests that there may be multiple pathways to HIV-1 resistance, influenced by factors such as the type of viral exposure, the immune environment, and individual genetics. Further research is needed to determine which immune states are protective and how these responses can be modulated to prevent infection.
尽管反复接触HIV-1会导致感染，但一些个体仍保持血清阴性，没有感染的临床或血清学证据；这些个体被称为HIV-1暴露血清阴性个体。为了解与HIV感染天然抗性相关的机制，对这一人群进行了广泛研究。已经提出了两种主要假说来解释这种抗性：一些研究人员将抗性与低激活表型相关联，其特征是与感染控制相关的免疫系统细胞的激活和增殖减少以及细胞因子和促炎分子的产生减少，而另一些人则认为抗性与免疫系统激活以及高水平趋化因子、促炎细胞因子和抗病毒分子的表达有关。
我们的研究旨在回顾和分析支持免疫系统激活水平在HIV-1感染天然抗性中作用的最相关证据。
通过PubMed、SciELO和ScienceDirect数据库进行检索。文献检索以非系统方式进行。回顾了过去五十年来发表的关于HIV天然抗性中免疫激活机制的文章。
低激活表型在外周和粘膜组织中以调节性T细胞频率高、CD25、CD38和HLA-DR表达降低以及促炎细胞因子产生较低为特征，在减少易感染的活化细胞数量方面起关键作用，但它使慢性炎症最小化，促进病毒进入和传播。相比之下，激活表型与CD25、CD38和HLA-DR等标志物的高表达以及高水平的干扰素刺激基因和促炎细胞因子升高有关。这种特征可以促进感染控制，同时增加病毒易感细胞的数量。
HIV暴露期间免疫反应的复杂性，反映在关于低免疫激活还是高免疫激活提供抗感染保护的相互矛盾的证据中，表明可能存在多种HIV-1抗性途径，受病毒暴露类型、免疫环境和个体遗传学等因素影响。需要进一步研究以确定哪些免疫状态具有保护作用以及如何调节这些反应以预防感染。
