Unidad de Enfermedades Infecciosas, Servicio de Medicina Interna, Hospital Universitario Puerta del Mar, Facultad de Medicina, Universidad de Cádiz, Instituto de Investigación e Innovación en Ciencias Biomédicas de Cádiz (INiBICA), Cádiz, Spain.
Servicio de Microbiología, Hospital Universitario Puerta del Mar, Facultad de Medicina, Universidad de Cádiz, Instituto de Investigación e Innovación en Ciencias Biomédicas de Cádiz (INiBICA), Cádiz, Spain.
Clin Exp Immunol. 2018 Dec;194(3):350-360. doi: 10.1111/cei.13201. Epub 2018 Sep 17.
The objective of this study was to conduct an analysis of peripheral blood Th17 cells with the ability to home to gut mucosa (CD4 Th17 β7 ) during recent or chronic human immunodeficiency virus (HIV) infections. The relationship between HIV load and systemic inflammation markers was studied. Twenty-five patients with recent (n = 10) or chronic (n = 15) untreated HIV infections; 30 treated HIV-infected patients with undetectable HIV load at the time of inclusion and 30 healthy controls were included. Bacterial translocation markers (16S rDNA), soluble CD14 (sCD14) and interleukin (IL)-6 monocyte activation parameters, CD4/CD8 ratio and T helper type 17 (Th17) subpopulations [CD4 Th17 expressing the IL-23 receptor (IL-23R) or β7] were analysed at baseline and after 6 and 12 months of anti-retroviral therapy (ART). 16S rDNA was detected in all patients. Significantly increased serum levels of sCD14 and IL-6 and a decreased CD4/CD8 ratio were observed in patients. Similar percentages of CD4 IL-23R and CD4 Th17 β7 cells were observed in healthy controls and patients at baseline. After 12 months of therapy, patients with a recent HIV infection showed significant increases of CD4 IL-23R and CD4 Th17 β7 cell percentages and a decrease in IL-6 levels, although 16S rDNA continued to be detectable in all patients. No significant differences were observed in Th17 subpopulations in patients with chronic HIV infection after therapy. Early initiation of ART helps to increase the number of Th17 cells with the ability to home to the intestinal mucosa and to partially restore gut mucosal homeostasis. These results provide a rationale for initiating ART during the acute phase of HIV infection.
本研究旨在分析近期或慢性人类免疫缺陷病毒(HIV)感染期间归巢至肠道黏膜的外周血 Th17 细胞(CD4 Th17β7)。研究了 HIV 载量与全身炎症标志物之间的关系。纳入了 25 例近期(n=10)或慢性(n=15)未经治疗的 HIV 感染患者;30 例接受治疗的 HIV 感染患者在纳入时 HIV 载量不可检测;以及 30 名健康对照者。在基线时和抗逆转录病毒治疗(ART)后 6 个月和 12 个月时分析了细菌易位标志物(16S rDNA)、可溶性 CD14(sCD14)和白细胞介素(IL)-6 单核细胞激活参数、CD4/CD8 比值和 T 辅助 17(Th17)亚群[表达白细胞介素-23 受体(IL-23R)或β7 的 CD4 Th17]。在所有患者中均检测到 16S rDNA。患者的血清 sCD14 和 IL-6 水平显著升高,CD4/CD8 比值降低。健康对照者和患者在基线时 CD4 IL-23R 和 CD4 Th17β7 细胞的百分比相似。经过 12 个月的治疗,近期 HIV 感染患者的 CD4 IL-23R 和 CD4 Th17β7 细胞百分比显著增加,IL-6 水平降低,尽管所有患者仍可检测到 16S rDNA。治疗后慢性 HIV 感染患者的 Th17 亚群无显著差异。早期启动 ART 有助于增加归巢至肠道黏膜的 Th17 细胞数量,并部分恢复肠道黏膜的稳态。这些结果为在 HIV 感染的急性期启动 ART 提供了依据。