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Immunosenescence in chronic HIV infected patients impairs essential functions of their natural killer cells.
International Immunopharmacology ( IF 5.6 ) Pub Date : 2020-05-11 , DOI: 10.1016/j.intimp.2020.106568
Luana Silva Soares 1 , Milena Sobral Espíndola 1 , Fabiana Albani Zambuzi 1 , Leonardo Judson Galvão-Lima 1 , Maira Costa Cacemiro 1 , Murilo Racy Soares 1 , Bárbara A Santana 2 , Rodrigo T Calado 2 , Valdes Roberto Bollela 3 , Fabiani Gai Frantz 1
Affiliation  

The HIV/AIDS pandemic still represents an important global health issue. There is no sterilizing cure, therefore a continuous treatment is necessary, which caused the emerged idea of HIV as a chronic inflammatory disease that may also affect healthy aging. Considering that the activation profile of some innate cells such as natural killer cells has previously been associated to HIV progression, it remains to be better defined this activation status of NK cells considering the time of HIV infection. In this study, we characterized NK cell phenotype and function during acute and chronic HIV infection and also investigated markers of immunosenescence in these cells. Our results showed that chronic infected patients remained with elevated levels of some plasma inflammatory molecules (IP-10, sCD14) and a concurrent expansion of the non-functional NK cell subset (CD3-CD56-CD16+). NK cells from the chronic infected group displayed an activated profile with higher levels of cytokines and chemokines production (TNF-α, IL-12, IFN-α2, IFN-γ, IL-6, RANTES, MCP-1, IL-10, IL-4 and IL-5). The production of these molecules was positively correlated to the time of infection. Moreover, we noted a possible association of higher global DNA methylation frequency of NK cells in two HIV patients in the advanced stage of disease. Chronic infected patients also showed a trend towards higher production of reactive oxygen species by their NK cells which altogether suggest the evolution of these cells to a senescent state that might be further evaluated.



中文翻译:

慢性HIV感染患者的免疫衰弱削弱了其自然杀伤细胞的基本功能。

艾滋病毒/艾滋病的流行仍然代表着重要的全球卫生问题。没有消毒方法,因此必须进行连续治疗,这导致出现了将HIV视为慢性炎性疾病的想法,这也可能影响健康的衰老。考虑到某些先天性细胞(例如自然杀伤细胞)的激活特性先前已与HIV进展相关,因此考虑到HIV感染的时间,仍需要更好地定义NK细胞的激活状态。在这项研究中,我们表征了急性和慢性HIV感染期间NK细胞的表型和功能,并研究了这些细胞中免疫衰老的标志物。我们的结果表明,慢性感染患者的血浆炎症分子(IP-10,- CD56 - CD16 +)。来自慢性感染组的NK细胞显示出较高水平的细胞因子和趋化因子生成的激活特征(TNF-α,IL-12,IFN-α2,IFN-γ,IL-6,RANTES,MCP-1,IL-10, IL-4和IL-5)。这些分子的产生与感染时间呈正相关。此外,我们注意到在两名处于疾病晚期的HIV患者中,NK细胞较高的全球DNA甲基化频率可能与其相关。慢性感染的患者还显示出其NK细胞产生更高的活性氧的趋势,这完全表明这些细胞向衰老状态的进化可能需要进一步评估。

更新日期:2020-05-11
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