Lu Danfeng, Zhang Jian-Bo, Wang Yue-Xin, Geng Shi-Tao, Zhang Zunyue, Xu Yu, Li Shao-You, Wang Kun-Hua, Kuang Yi-Qun
NHC Key Laboratory of Drug Addiction Medicine, First Affiliated Hospital of Kunming Medical University, Kunming Medical University, 295 Xichang Road, Kunming, Yunnan, China.
Scientific Research Laboratory Center, First Affiliated Hospital of Kunming Medical University, Kunming, China.
BMC Infect Dis. 2021 Aug 3;21(1):742. doi: 10.1186/s12879-021-06491-z.
CD4 T cell counts in certain human immunodeficiency virus (HIV)-infected patients called immunological non-responders (INRs) could not return to a normal level even with sustained antiretroviral therapy (ART) because of persistent immune activation, which is associated with pro-inflammatory cytokines production and an altered intestinal microbiome profile. Changes in gut bacterial composition have been linked to low CD4 T cell counts in HIV-infected individuals. However, the association between CD4 T cell counts and gut microbiota community composition and cytokines levels in INRs (CD4 T cell counts < 500 cells/μL) from Yunnan Province, China, has not been previously investigated.
To address this issue, we carried out a cross-sectional study of 34 HIV-infected INRs. The patients were divided into CD4 count > 200 cells/μL group and CD4 count < 200 cells/μL group. The gut microbiota composition of each subject was analyzed by 16S rRNA gene sequencing. We also compared CD8 T cell counts, pro-inflammatory cytokines levels, and nutritional status between the two groups.
Compared to INRs with CD4 count > 200 cells/μL, those with CD4 count < 200 cells/μL had a lower CD4/CD8 ratio, lower nutritional status and higher serum levels of tumor necrosis factor (TNF)-α, interferon-γ-inducible protein (IP)-10 and interleukin (IL)-1α. Ruminococcaceae was less abundant in the CD4 count < 200 cells/μL group than in the CD4 count > 200 cells/μL group, and difference in alpha diversity was observed between the two groups. Moreover, CD4 T cell counts were negatively associated with TNF-α and IL-1α levels and positively associated with the relative abundance of Ruminococcaceae.
Our study demonstrated that lower CD4 T cell counts in INRs are associated with a reduced abundance of Ruminococcaceae in the gut and elevated serum pro-inflammatory cytokines levels. Thus, interventions targeting gut microbiota to increase CD4 T cell counts are a potential strategy for promoting immune reconstitution in HIV-infected INRs.
某些被称为免疫无应答者（INRs）的人类免疫缺陷病毒（HIV）感染患者，即使接受持续的抗逆转录病毒疗法（ART），其CD4 T细胞计数也无法恢复到正常水平，原因是持续的免疫激活，这与促炎细胞因子的产生以及肠道微生物群谱的改变有关。肠道细菌组成的变化与HIV感染个体的低CD4 T细胞计数有关。然而，中国云南省免疫无应答者（CD4 T细胞计数<500个细胞/μL）的CD4 T细胞计数与肠道微生物群组成及细胞因子水平之间的关联此前尚未得到研究。
为解决这一问题，我们对34名HIV感染的免疫无应答者进行了一项横断面研究。患者被分为CD4计数>200个细胞/μL组和CD4计数<200个细胞/μL组。通过16S rRNA基因测序分析每个受试者的肠道微生物群组成。我们还比较了两组之间的CD8 T细胞计数、促炎细胞因子水平和营养状况。
与CD4计数>200个细胞/μL的免疫无应答者相比，CD4计数<200个细胞/μL的免疫无应答者的CD4/CD8比值更低、营养状况更差，血清肿瘤坏死因子（TNF）-α、干扰素-γ诱导蛋白（IP）-10和白细胞介素（IL）-1α水平更高。CD4计数<200个细胞/μL组的瘤胃球菌科丰度低于CD4计数>200个细胞/μL组，且两组之间观察到α多样性差异。此外，CD4 T细胞计数与TNF-α和IL-1α水平呈负相关，与瘤胃球菌科的相对丰度呈正相关。
我们的研究表明，免疫无应答者中较低的CD4 T细胞计数与肠道中瘤胃球菌科丰度降低以及血清促炎细胞因子水平升高有关。因此，针对肠道微生物群以增加CD4 T细胞计数的干预措施是促进HIV感染的免疫无应答者免疫重建的一种潜在策略。
