Clinical Infection Medicine, Department of Translational Medicine, Lund Universitygrid.4514.4, Malmö, Sweden.
Armauer Hansen Research Institute, Addis Ababa, Ethiopia.
Microbiol Spectr. 2022 Oct 26;10(5):e0117822. doi: 10.1128/spectrum.01178-22. Epub 2022 Aug 15.
The immune control of tuberculosis (TB) infection could be influenced by pregnancy. To elucidate this, we longitudinally characterized Mycobacterium tuberculosis (Mtb)-specific and nonspecific immune responses in women during pregnancy and postpartum. HIV-uninfected women without past or current active TB, and with blood samples available from the 1st/2nd trimester, 3rd trimester, and 9 months postpartum, were identified at Ethiopian antenatal care clinics. Twenty-two TB+ women and 10 TB- women, defined according to Mtb-stimulated interferon-γ levels (≥0.35 and <0.20 IU/mL, respectively, in the Quantiferon-TB Gold-Plus assay), were included in the study. Longitudinal dynamics of six cytokines (IL-1ra, IL-2, IP-10, MCP-2, MCP-3, and TGF-β1) were analyzed in supernatants from Mtb-stimulated and unstimulated whole blood. In TB+ women, Mtb-specific expression of IL-2 and IP-10 was higher at 3rd compared to 1st/2nd trimester (median 139 pg/mL versus 62 pg/mL, = 0.006; 4,999 pg/mL versus 2,310 pg/mL, = 0.031, respectively), whereas level of Mtb-triggered TGF-β1 was lower at 3rd compared to 1st/2nd trimester (-6.8 ng/mL versus 2.3 ng/mL, = 0.020). Unstimulated IL-2, IP-10, and MCP-2 levels were increased postpartum, compared with those noted during pregnancy, in TB+ women. Additionally, postpartum levels of proinflammatory cytokines in unstimulated blood were higher in TB+ women, than in TB- women. None of the women developed active TB during follow-up. Taken together, dynamic changes of Mtb-specific cytokine expression revealed during the 3rd trimester in TB+ women indicate increased Mtb-antigen stimulation at later stages of pregnancy. This could reflect elevated bacterial activity, albeit without transition to active TB, during pregnancy. Tuberculosis (TB) is globally one of the most common causes of death, and a quarter of the world's population is estimated to have TB infection. The risk of active TB is increased in connection to pregnancy, a phenomenon that could be due to physiological immune changes. Here, we studied the effect of pregnancy on immune responses triggered in HIV-uninfected women with TB infection, by analyzing blood samples obtained longitudinally during pregnancy and after childbirth. We found that the dynamics of Mtb-specific and nonspecific immune responses changed during pregnancy, especially in later stages of pregnancy, although none of the women followed in this study developed active TB. This suggests that incipient TB, with elevated bacterial activity, occurs during pregnancy, but progression of infection appears to be counteracted by Mtb-specific immune responses. Thus, this study sheds light on immune control of TB during pregnancy, which could be of importance for future intervention strategies.
结核病（TB）感染的免疫控制可能受到怀孕的影响。为了阐明这一点，我们在怀孕期间和产后纵向描述了结核分枝杆菌（Mtb）特异性和非特异性免疫反应。在埃塞俄比亚产前保健诊所确定了未感染 HIV 的孕妇，她们没有过去或现在的活动性结核病，并且在第 1/2 孕期、第 3 孕期和产后 9 个月有血液样本。根据 Mtb 刺激的干扰素-γ水平（定量干扰素-TB 金加检测分别为≥0.35 和 <0.20IU/mL），将 22 名 TB+妇女和 10 名 TB-妇女纳入研究。分析了 Mtb 刺激和未刺激全血上清液中六种细胞因子（IL-1ra、IL-2、IP-10、MCP-2、MCP-3 和 TGF-β1）的纵向动态。与第 1/2 孕期相比，第 3 孕期时，TB+妇女的 Mtb 特异性 IL-2 和 IP-10 表达更高（中位数分别为 139pg/mL 与 62pg/mL， = 0.006；4999pg/mL 与 2310pg/mL， = 0.031），而 Mtb 触发的 TGF-β1 水平在第 3 孕期则较低（与第 1/2 孕期相比为-6.8ng/mL 与 2.3ng/mL， = 0.020）。与怀孕期间相比，TB+妇女产后未刺激的 IL-2、IP-10 和 MCP-2 水平升高。此外，与 TB-妇女相比，TB+妇女产后未刺激的促炎细胞因子水平更高。在随访期间，没有妇女发生活动性结核病。综上所述，在 TB+妇女中，第 3 孕期 Mtb 特异性细胞因子表达的动态变化表明，在妊娠晚期，Mtb 抗原刺激增加。这可能反映了妊娠期间细菌活性增加，尽管没有过渡到活动性结核病。
结核病（TB）是全球最常见的死因之一，估计世界上四分之一的人口患有结核病感染。与怀孕有关的活动性结核病风险增加，这一现象可能是由于生理免疫变化所致。在这里，我们通过分析在怀孕期间和产后获得的纵向血液样本，研究了怀孕对感染结核分枝杆菌的 HIV 阴性妇女免疫反应的影响。我们发现，Mtb 特异性和非特异性免疫反应的动态在怀孕期间发生变化，尤其是在妊娠晚期，尽管在这项研究中随访的妇女都没有发展为活动性结核病。这表明，潜伏性结核病（细菌活性升高）发生在怀孕期间，但感染的进展似乎被 Mtb 特异性免疫反应所抑制。因此，这项研究揭示了怀孕期间结核病的免疫控制，这可能对未来的干预策略很重要。
