Makerere University, Walter Reed Project, P.O Box 16524, Kampala, Uganda.
Department of Pathology and Microbiology, University of Nebraska Medical Center, Omaha, NE, USA.
BMC Complement Med Ther. 2021 Apr 9;21(1):114. doi: 10.1186/s12906-021-03288-0.
In Sub-Saharan Africa, herbal therapy continues to be utilized for HIV-1 disease management. However, the therapeutic benefits of these substances remain ambiguous. To date, little is known about the effects of these plant extracts on chronic CD4 + T-cell activation and exhaustion which is partly driven by HIV-1 associated microbial translocation.
Effects of Azadirachta indica, Momordica foetida and Moringa oleifera ethanol: water mixtures on cell viability were evaluated using the Guava PCA system. Then, an in-vitro cell culture model was developed to mimic CD4+ T cell exposures to antigens following HIV-1 microbial translocation. In this, peripheral blood mononuclear cells (PBMCs) isolated from HIV negative (n = 13), viral load < 1000 copies per mL (n = 10) and viral load > 1000 copies per mL (n = 6) study participants from rural Uganda were treated with Staphylococcus enterotoxin B (SEB). Then, the candidate plant extract (A. indica) was added to test the potential to inhibit corresponding CD4+ T cell activation. Following BD Facs Canto II event acquisition, variations in %CD38, %CD69, Human Leukocyte Antigen -DR (HLA-DR), Programmed cell death protein 1 (PD-1), T-cell immunoglobulin and mucin domain-containing protein 3 (Tim-3), interferon gamma (IFN γ) and interleukin 2 (IL-2) CD4 + T cell expression were evaluated.
Following exposure to SEB, only A. indica demonstrated a concentration-dependent ability to downregulate the levels of CD4 + T cell activation. At the final concentration of 0.500 μg/mL of A. indica, a significant downregulation of CD4 + CD38 + HLA-DR+ expression was observed in HIV negative (p < 0.0001) and both HIV infected groups (P = 0.0313). This plant extract also significantly lowered SEB induced % CD4+ T cell HLADR, PD-1 and Tim-3 levels. PD-1 and CD69 markers were only significantly downmodulated in only the HIV negative ((p = 0.0001 and p = 0.0078 respectively) and viral load< 1000 copies per ml (p = 0.0078) groups.
A. indica exhibited the in-vitro immunomodulatory potential to inhibit the continuum of SEB induced CD4+ T-cell activation/ exhaustion without impacting general T-cell specific functions such as cytokine secretion. Additional studies are needed to confirm A. indica as a source of natural products for targeting persistent immune activation and inflammation during ART.
在撒哈拉以南非洲，草药疗法继续被用于治疗 HIV-1 疾病。然而，这些物质的治疗益处仍然存在争议。迄今为止，人们对这些植物提取物对慢性 CD4+T 细胞激活和衰竭的影响知之甚少，而这种激活和衰竭部分是由 HIV-1 相关的微生物易位引起的。
使用 Guava PCA 系统评估印楝、苦瓜和辣木乙醇：水混合物对细胞活力的影响。然后，建立了一种体外细胞培养模型，模拟 HIV-1 微生物易位后 CD4+T 细胞暴露于抗原。在这种情况下，从乌干达农村地区分离出 HIV 阴性（n=13）、病毒载量<1000 拷贝/ml（n=10）和病毒载量>1000 拷贝/ml（n=6）的研究参与者的外周血单核细胞（PBMC）用葡萄球菌肠毒素 B（SEB）处理。然后，加入候选植物提取物（印楝）以测试抑制相应 CD4+T 细胞激活的潜力。在 BD Facs Canto II 事件采集后，评估 CD38+、CD69+、人类白细胞抗原-DR（HLA-DR）、程序性细胞死亡蛋白 1（PD-1）、T 细胞免疫球蛋白和粘蛋白结构域蛋白 3（Tim-3）、干扰素γ（IFNγ）和白细胞介素 2（IL-2）的表达。
SEB 暴露后，只有印楝表现出浓度依赖性下调 CD4+T 细胞激活水平的能力。在印楝的最终浓度为 0.500μg/mL 时，在 HIV 阴性（p<0.0001）和所有 HIV 感染组（P=0.0313）中观察到 CD4+T 细胞 CD38+ HLA-DR+表达的显著下调。这种植物提取物还显著降低了 SEB 诱导的 CD4+T 细胞 HLA-DR、PD-1 和 Tim-3 水平。PD-1 和 CD69 标志物仅在 HIV 阴性（p=0.0001 和 p=0.0078）和病毒载量<1000 拷贝/ml（p=0.0078）组中显著下调。
印楝在体外具有免疫调节潜力，可抑制 SEB 诱导的 CD4+T 细胞激活/衰竭的连续过程，而不影响细胞因子分泌等一般 T 细胞特定功能。需要进一步的研究来确认印楝作为一种天然产物的来源，以针对 ART 期间持续的免疫激活和炎症。
