Translational Research Unit, National Institute for Infectious Diseases Lazzaro Spallanzani-IRCCS, Rome, Italy.
Department of Epidemiology, National Institute for Infectious Diseases Lazzaro Spallanzani-IRCCS, Rome, Italy.
Int J Infect Dis. 2024 Apr;141S:106999. doi: 10.1016/j.ijid.2024.106999. Epub 2024 Mar 7.
To investigate whether Mycobacterium tuberculosis (Mtb) DNA is detected in peripheral blood mononuclear cells (PBMC) of subjects with tuberculosis (TB) or TB infection (TBI) living in a low-burden country.
We prospectively enrolled 57 patients with TB, 41 subjects with TBI, and 39 controls in Rome, Italy. PBMC were isolated, cluster of differentiation (CD)34 and CD34 cells were immunomagnetic separated, DNA was extracted, and digital polymerase chain reaction for IS6110 and rpoB sequences was used to detect Mtb DNA in PBMC subsets and unfractionated PBMC.
We detected Mtb DNA at a low copy number in CD34 cells in 4o f 30 (13%) patients with TB, 2 of 24 (8%) subjects with TBI, and 1 of 24 (4%) controls. Mtb DNA was detected in unfractionated PBMC in 3 of 51 (6%) patients with TB, 2 of 38 (5%) subjects with TBI, and 2 of 36 (6%) controls. In CD34 cells, only 1 of 31 (3%) subjects with TBI tested positive for Mtb DNA.
Mtb DNA was detected at low frequencies and levels in the PBMC of subjects with TBI and donors with TB living in a low-burden country. In particular, Mtb DNA was detected more frequently in CD34 cells, supporting the hypothesis that these cells may represent a Mtb niche. This finding informs biological understanding of Mtb pathogenesis and may support the development of a microbial blood biomarker for Mtb infection.
研究低负担国家中结核病（TB）或结核感染（TBI）患者外周血单个核细胞（PBMC）中是否存在结核分枝杆菌（Mtb）DNA。
我们前瞻性地招募了 57 名结核病患者、41 名结核感染患者和 39 名对照者，来自意大利罗马。分离 PBMC，用免疫磁珠分离 CD34 和 CD34 细胞，提取 DNA，并用数字聚合酶链反应检测 IS6110 和 rpoB 序列，以检测 PBMC 亚群和未分馏的 PBMC 中的 Mtb DNA。
我们在 30 名结核病患者中的 4 名（13%）、24 名结核感染患者中的 2 名（8%）和 24 名对照者中的 1 名（4%）的 CD34 细胞中检测到 Mtb DNA，其拷贝数较低。在 51 名结核病患者中的 3 名（6%）、38 名结核感染患者中的 2 名（5%）和 36 名对照者中的 2 名（6%）的未分馏 PBMC 中检测到 Mtb DNA。在 CD34 细胞中，只有 24 名结核感染患者中的 1 名（3%）检测到 Mtb DNA 阳性。
在低负担国家中，TBI 患者和 TB 患者的 PBMC 中 Mtb DNA 的检出率和水平均较低。特别是在 CD34 细胞中更频繁地检测到 Mtb DNA，支持这些细胞可能代表 Mtb 生态位的假说。这一发现为 Mtb 发病机制的生物学理解提供了信息，并可能支持开发 Mtb 感染的微生物血液生物标志物。
