肠道菌群失调与HIV病毒抑制人群的细胞因子产生能力相关。
Gut dysbiosis associates with cytokine production capacity in viral-suppressed people living with HIV.
发表日期：2023
作者：
Yue Zhang, Sergio Andreu-Sánchez, Nadira Vadaq, Daoming Wang, Vasiliki Matzaraki, Wouter A van der Heijden, Ranko Gacesa, Rinse K Weersma, Alexandra Zhernakova, Linos Vandekerckhove, Quirijn de Mast, Leo A B Joosten, Mihai G Netea, André J A M van der Ven, Jingyuan Fu
来源：
CYTOKINE & GROWTH FACTOR REVIEWS
摘要：
人类免疫缺陷病毒（PLHIV）患者即使通过抗逆转录病毒治疗（ART）抑制了病毒复制，也会暴露于慢性免疫失调的影响之下。鉴于肠道菌群在免疫中的新兴作用，我们假设肠道菌群可能与PLHIV的细胞因子产生能力相关。为验证这一假设，我们收集了143个ART治疗过的PLHIV的宏基因组数据，并评估了他们对不同刺激物的体外产生8种不同细胞因子（白细胞介素-1β（IL-1β）、IL-6、IL-1Ra、IL-10、IL-17、IL-22、肿瘤坏死因子和干扰素-γ）的能力。我们还对CD4+ T细胞计数、HIV潜藏库以及其他临床指标进行了表征。与190个年龄和性别匹配的对照组及第二个独立对照队列相比，PLHIV表现出与病毒库水平（CD4+ T细胞相关的HIV-1 DNA）、细胞因子产生能力和性行为相关的菌群失调现象。值得注意的是，我们鉴定出两个基因不同的P. copri菌株，分别富集于PLHIV或健康对照组。与PLHIV相关的菌株相比，与对照组相关的菌株与细胞因子产生能力之间的负相关性更强，尤其是Pam3Cys诱导的IL-6和IL-10产生。与对照组相关的菌株还与CD4+ T细胞水平呈正相关。我们的研究结果表明，调节肠道菌群可能是调控PLHIV免疫反应的策略。Copyright © 2023 Zhang, Andreu-Sánchez, Vadaq, Wang, Matzaraki, van der Heijden, Gacesa, Weersma, Zhernakova, Vandekerckhove, de Mast, Joosten, Netea, van der Ven and Fu.
People living with human immunodeficiency virus (PLHIV) are exposed to chronic immune dysregulation, even when virus replication is suppressed by antiretroviral therapy (ART). Given the emerging role of the gut microbiome in immunity, we hypothesized that the gut microbiome may be related to the cytokine production capacity of PLHIV.To test this hypothesis, we collected metagenomic data from 143 ART-treated PLHIV and assessed the ex vivo production capacity of eight different cytokines [interleukin-1β (IL-1β), IL-6, IL-1Ra, IL-10, IL-17, IL-22, tumor necrosis factor, and interferon-γ] in response to different stimuli. We also characterized CD4+ T-cell counts, HIV reservoir, and other clinical parameters.Compared with 190 age- and sex-matched controls and a second independent control cohort, PLHIV showed microbial dysbiosis that was correlated with viral reservoir levels (CD4+ T-cell-associated HIV-1 DNA), cytokine production capacity, and sexual behavior. Notably, we identified two genetically different P. copri strains that were enriched in either PLHIV or healthy controls. The control-related strain showed a stronger negative association with cytokine production capacity than the PLHIV-related strain, particularly for Pam3Cys-incuded IL-6 and IL-10 production. The control-related strain is also positively associated with CD4+ T-cell level.Our findings suggest that modulating the gut microbiome may be a strategy to modulate immune response in PLHIV.Copyright © 2023 Zhang, Andreu-Sánchez, Vadaq, Wang, Matzaraki, van der Heijden, Gacesa, Weersma, Zhernakova, Vandekerckhove, de Mast, Joosten, Netea, van der Ven and Fu.