DSI-NRF Centre of Excellence for Biomedical Tuberculosis Research, South African Medical Research Council Centre for Tuberculosis Research, and Division of Molecular Biology and Human Genetics, Faculty of Medicine and Health Sciences, Stellenbosch University, Cape Town, South Africa.
Public Health Research Institute, New Jersey Medical School, Rutgers, The State University of New Jersey, Newark, New Jersey, USA.
J Interferon Cytokine Res. 2022 Apr;42(4):141-152. doi: 10.1089/jir.2021.0216. Epub 2022 Feb 14.
Cytokines have an important role in mounting effective host immune response against mycobacteria. Latent tuberculosis infection (LTBI) is an indication of containment of mycobacteria by the host immune response, whereas active TB is an indication of a failure of the immune response to contain . The dynamics of this host-immune response during infection experiment is believed to be indicative of behavior in the LTBI and active-TB cases. This relationship is, however, not fully elucidated. We investigated the cytokines expression at mRNA and protein level across 2 different protocols, that is, an protocol comparing human monocyte-derived macrophages (hMDMs; = 12) infected with different species of mycobacteria, and a clinical protocol comparing TB-Antigen-Nil specimens from LTBI ( = 12) and active-TB ( = 12) cases. We found that infection of hMDMs with Bacillus Calmette-Guérin (BCG) and R179 showed increased colony-forming units at all time points postinfection. BCG-infected hMDMs demonstrated higher levels of 5 cytokines [interferon (IFN)-γ, interleukin (IL)-6, IL-1β, IL-12p40, and IL-12p70] at different intervals compared to R179. Compared to LTBI, active-TB cases had higher mRNA expression of IFN-α, IL-6, and IL-8, and lower expression of IFN-γ, IL-1α, IL-1β, IL-4, and tumor necrosis factor-α. Overall, we observed differential host responses at mRNA and protein levels during experimentally controlled infection, but no prominent differences were observed in the clinical protocol. Therefore, the result of the experiment model of cytokine response against mycobacteria should be interpreted cautiously when relating to LTBI and active-TB.
细胞因子在宿主对分枝杆菌产生有效免疫反应方面发挥着重要作用。潜伏性结核感染(LTBI)表明宿主免疫反应对分枝杆菌的控制,而活动性结核病则表明免疫反应未能控制。感染实验中宿主免疫反应的动态被认为是 LTBI 和活动性结核病病例行为的指示。然而,这种关系尚未完全阐明。我们在两种不同方案中(即比较感染不同种分枝杆菌的人单核细胞衍生巨噬细胞(hMDM)的方案和比较 LTBI 和活动性结核病病例的 TB 抗原阴性标本的方案),在 mRNA 和蛋白水平上检测了细胞因子的表达。我们发现,hMDM 感染卡介苗(BCG)和 R179 后,所有时间点的集落形成单位(CFU)均增加。与 R179 相比,BCG 感染的 hMDM 在不同时间间隔显示出更高水平的 5 种细胞因子(IFN-γ、IL-6、IL-1β、IL-12p40 和 IL-12p70)。与 LTBI 相比,活动性结核病病例的 IFN-α、IL-6 和 IL-8 的 mRNA 表达更高,而 IFN-γ、IL-1α、IL-1β、IL-4 和肿瘤坏死因子-α的表达更低。总体而言,我们在实验性控制感染过程中观察到宿主在 mRNA 和蛋白水平上的不同反应,但在临床方案中未观察到明显差异。因此,当涉及 LTBI 和活动性结核病时,应谨慎解释分枝杆菌细胞因子反应实验模型的结果。