Department of Public Health and Infectious Diseases.
Laboratory of Virology, Department of Molecular Medicine, Istituto Pasteur Italia, Sapienza University, Rome.
AIDS. 2020 Aug 1;34(10):1467-1473. doi: 10.1097/QAD.0000000000002574.
HIV-1-associated dysbiosis is most commonly characterized by overall decreased diversity, with abundance of the genus Prevotella, recently related to inflammatory responses.
A pilot study including 10 antiretroviral therapy-treated HIV-1-infected men and 50 uninfected controls was performed to identify the main gut dysbiosis determinants (e.g. Prevotella enrichment), that may affect mucosal antiviral defenses and T cell immunity in HIV-1-infected individuals.
16rRNA gene sequencing was applied to the HIV-1-infected individuals' fecal microbiota and compared with controls. Measurements of CD4 and CD8 T cell activation [CD38, human leukocyte antigen (HLA)-DR, CD38 HLA-DR] and frequencies of Th17, obtained from lamina propria lymphocytes isolated from five different intestinal sites, were performed by flow cytometry. IFNβ, IFNAR1 and MxA gene expression level was evaluated by real-time PCR in lamina propria lymphocytes. Nonparametric t tests were used for statistical analysis.
HIV-1-infected men had a significant fecal microbial communities' imbalance, including different levels of genera Faecalibacterium, Prevotella, Alistipes and Bacteroides, compared with controls. Notably, Prevotella abundance positively correlated with frequencies of CD4 T cells expressing CD38 or HLA-DR and coexpressing CD38 and HLA-DR (P < 0.05 for all these measures). The same trend was observed for the activated CD8 T cells. Moreover, Prevotella levels were inversely correlated with IFN-I genes (P < 0.05 for IFNβ, IFNAR1 and MxA genes) and the frequencies of Th17 cells (P < 0.05). By contrast, no statistically significant correlations were observed for the remaining bacterial genera.
Our findings suggest that Prevotella enrichment might affect gut mucosal IFN-I pathways and T cell response in HIV-1-infected patients, thus contributing to immune dysfunction.
HIV-1 相关的菌群失调最常见的特征是总体多样性降低，丰度增加的普雷沃氏菌属与炎症反应有关。
进行了一项包括 10 名接受抗逆转录病毒治疗的 HIV-1 感染男性和 50 名未感染对照的试点研究，以确定主要的肠道菌群失调决定因素（例如普雷沃氏菌属的富集），这些因素可能影响 HIV-1 感染者的黏膜抗病毒防御和 T 细胞免疫。
应用 16rRNA 基因测序对 HIV-1 感染个体的粪便微生物群进行分析，并与对照进行比较。通过流式细胞术测量从五个不同肠道部位分离的固有层淋巴细胞中 CD4 和 CD8 T 细胞的激活[CD38、人类白细胞抗原（HLA）-DR、CD38 HLA-DR]和 Th17 频率。通过实时 PCR 评估固有层淋巴细胞中 IFNβ、IFNAR1 和 MxA 基因的表达水平。使用非参数 t 检验进行统计分析。
与对照组相比，HIV-1 感染男性的粪便微生物群落失衡明显，包括不同水平的 Faecalibacterium、Prevotella、Alistipes 和 Bacteroides 属。值得注意的是，Prevotella 的丰度与表达 CD38 或 HLA-DR 的 CD4 T 细胞以及同时表达 CD38 和 HLA-DR 的 CD4 T 细胞的频率呈正相关（所有这些指标的 P 值均＜0.05）。这种趋势也存在于激活的 CD8 T 细胞中。此外，Prevotella 水平与 IFN-I 基因（IFNβ、IFNAR1 和 MxA 基因，P 值均＜0.05）和 Th17 细胞的频率呈负相关（P 值均＜0.05）。相比之下，其余细菌属之间没有观察到统计学上显著的相关性。
我们的研究结果表明，普雷沃氏菌属的富集可能影响 HIV-1 感染患者的肠道黏膜 IFN-I 途径和 T 细胞反应，从而导致免疫功能障碍。
