Department of Internal Medicine, The Second School of Clinical Medicine, Southern Medical University, Guangzhou, China.
Senior Department of Infectious Diseases, the Fifth Medical Center of Chinese PLA General Hospital, National Clinical Research Center for Infectious Diseases, Beijing, China.
Viral Immunol. 2023 Jun;36(5):331-342. doi: 10.1089/vim.2023.0017. Epub 2023 May 15.
Studies assessing the gut mucosal immune balance in HIV-infected patients using intestinal samples are scarce. In this study, we used intestinal mucosal specimens from the ileocecal region of seven immunological nonresponders (INRs), nine immunological responders (IRs), and six HIV-negative controls. We investigated T helper 17 (Th17) and T regulatory (Treg) cell counts and their ratio, zonula occludens-1 (ZO-1), intestinal fatty acid-binding protein (I-FABP), tumor necrosis factor-α, CD4 T cell counts, HIV DNA, and cell-associated HIV RNA. The results showed that INRs had lower Th17 and higher Treg cell counts than IR, resulting in a significant difference in the Th17/Treg ratio between IRs and INRs. In addition, INRs had lower ZO-1 and higher I-FABP levels than IRs. The Th17/Treg ratio was positively associated with ZO-1 and negatively associated with I-FABP levels. There was a positive correlation between Th17/Treg ratio and CD4 T cell counts and a negative correlation between the Th17/Treg ratio and HIV DNA in the intestine. Our study suggests that the imbalance of Th17/Treg in the intestine is a characteristic of incomplete immune reconstitution to antiretroviral therapy and is associated with intestinal damage.
利用肠道样本评估 HIV 感染患者肠道黏膜免疫平衡的研究较为匮乏。在本研究中,我们使用了 7 名免疫无应答者(INRs)、9 名免疫应答者(IRs)和 6 名 HIV 阴性对照者的回肠末端黏膜标本。我们检测了 Th17 和 T 调节(Treg)细胞计数及其比值、闭合蛋白-1(ZO-1)、肠脂肪酸结合蛋白(I-FABP)、肿瘤坏死因子-α、CD4 T 细胞计数、HIV 病毒载量和细胞相关 HIV RNA。结果表明,与 IR 相比,INRs 的 Th17 细胞计数较低,Treg 细胞计数较高,导致 IR 和 INR 之间的 Th17/Treg 比值存在显著差异。此外,与 IR 相比,INRs 的 ZO-1 水平较低,I-FABP 水平较高。Th17/Treg 比值与 ZO-1 呈正相关,与 I-FABP 水平呈负相关。Th17/Treg 比值与肠道 CD4 T 细胞计数呈正相关,与肠道 HIV 病毒载量呈负相关。我们的研究表明,肠道中 Th17/Treg 的失衡是抗逆转录病毒治疗不完全免疫重建的特征,与肠道损伤有关。