Dasan Bindu, Rajamanickam Anuradha, Pandiarajan Arul Nancy, Shanmugam Sivakumar, Nott Sujatha, Babu Subash
Department of ICER, National Institute of Health-National Institute of Allergy and Infectious Diseases-International Center for Excellence in Research, Chennai, India.
Department of Bacteriology, ICMR-National Institute for Research in Tuberculosis, Chennai, India.
Microbiol Spectr. 2025 Jan 7;13(1):e0144524. doi: 10.1128/spectrum.01445-24. Epub 2024 Dec 10.
Several studies have highlighted the increased risk of active tuberculosis (TB) in individuals with diabetes mellitus (DM), especially in TB-endemic regions. This dual burden poses significant challenges for TB control efforts. However, there is a lack of reliable laboratory tools to identify individuals at higher risk, and the immunological mechanisms underlying this susceptibility are poorly understood. In this study, we utilized the mycobacterial growth inhibition assay (MGIA) to assess immune response capacity against () in TB infection (TBI) in individuals with type 2 DM (T2DM) ( = 11) compared to those without type 2 DM (NDM) ( = 23). Additionally, we measured various cytokines using multiplex ELISA to understand the immune profile. Our findings revealed that TBI-T2DM individuals exhibited a lower capacity to inhibit growth compared to TBI-NDM, as evidenced by MGIA results ( = 0.0029). Cytokine analysis further demonstrated diminished production of key cytokines involved in protection, including type 1 (IFNγ, TNFα, IL-2), type 17 (IL-17A), and proinflammatory (IL-1α, IL-1β, IL-6, IL-12p70) cytokines in the TBI-T2DM group compared to TBI-NDM, upon infection. These findings suggest that MGIA holds promise as an marker for assessing immunological control in TBI individuals, particularly those with T2DM. The observed cytokine profile in TBI-T2DM individuals indicates a compromised immune response against activation, potentially explaining the heightened risk of active TB in this population.
This study is important because it sheds light on the impaired immune response in individuals with type 2 diabetes mellitus (T2DM) who are infected with Mycobacterium tuberculosis (M.tb), offering critical insights into why they are at higher risk of developing active tuberculosis (TB). By demonstrating that T2DM individuals exhibit a weakened ability to control M.tb growth and a compromised cytokine profile, the research underscores the need for better diagnostic tools, such as the mycobacterial growth inhibition assay (MGIA), to identify those at greater risk of progression to active TB. The findings also highlight the importance of integrated care strategies for managing both T2DM and TB, particularly in TB-endemic regions, and point to the need for further research to develop more effective interventions tailored to this vulnerable population.
多项研究强调了糖尿病（DM）患者发生活动性结核病（TB）的风险增加，尤其是在结核病流行地区。这种双重负担给结核病控制工作带来了重大挑战。然而，缺乏可靠的实验室工具来识别高风险个体，而且对这种易感性的免疫机制了解甚少。在本研究中，我们利用分枝杆菌生长抑制试验（MGIA）评估了2型糖尿病（T2DM）患者（n = 11）与非2型糖尿病（NDM）患者（n = 23）在结核感染（TBI）中针对（）的免疫反应能力。此外，我们使用多重ELISA检测了多种细胞因子，以了解免疫谱。我们的研究结果显示，与TBI-NDM患者相比，TBI-T2DM患者抑制（）生长的能力较低，MGIA结果证明了这一点（P = 0.0029）。细胞因子分析进一步表明，与TBI-NDM患者相比，在感染（）后，TBI-T2DM组中参与保护的关键细胞因子的产生减少，包括1型（IFNγ、TNFα、IL-2）、17型（IL-17A）和促炎（IL-1α、IL-1β、IL-6、IL-12p70）细胞因子。这些发现表明，MGIA有望作为评估TBI个体，特别是T2DM个体中（）免疫控制的标志物。在TBI-T2DM个体中观察到的细胞因子谱表明针对（）激活的免疫反应受损，这可能解释了该人群中活动性结核病风险增加的原因。
本研究很重要，因为它揭示了感染结核分枝杆菌（M.tb）的2型糖尿病（T2DM）患者免疫反应受损的情况，为他们为何患活动性结核病（TB）的风险更高提供了关键见解。通过证明T2DM个体控制M.tb生长的能力减弱且细胞因子谱受损，该研究强调需要更好的诊断工具，如分枝杆菌生长抑制试验（MGIA），以识别那些进展为活动性TB风险更高的个体。研究结果还突出了综合护理策略对管理T2DM和TB的重要性，特别是在结核病流行地区，并指出需要进一步研究以开发针对这一脆弱人群的更有效干预措施。
