Impact of Intermediate Hyperglycemia and Diabetes on Immune Dysfunction in Tuberculosis.
Impact of Intermediate Hyperglycemia and Diabetes on Immune Dysfunction in Tuberculosis.
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DOI：
10.1093/cid/ciaa751
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发表时间：
2021-01-23
期刊：
影响因子：
--
通讯作者：
TANDEM consortium
中科院分区：
文献类型：
--
作者：
Eckold C;Kumar V;Weiner J;Alisjahbana B;Riza AL;Ronacher K;Coronel J;Kerry-Barnard S;Malherbe ST;Kleynhans L;Stanley K;Ruslami R;Ioana M;Ugarte-Gil C;Walzl G;van Crevel R;Wijmenga C;Critchley JA;Dockrell HM;Cliff JM;TANDEM consortium
糖尿病患者患活动性结核病（TB）的风险增加，并且更有可能具有不良TB治疗结果，这可能会影响TB的控制，因为糖尿病的患病率在全球范围内增加。相对于健康个体，活动性TB患者的血液转录组发生改变。研究了糖尿病和中度高血糖（IH）对该转录组特征的影响，以增强对糖尿病-TB合并症免疫易感性的理解。从4个国家（南非、罗马尼亚、印度尼西亚和秘鲁）的糖尿病（糖化血红蛋白[HbA 1c] ≥6.5%）或IH（HbA 1c = 5.7%至<6.5%）活动性TB患者、仅TB患者和健康对照者中采集全血样本。通过RNA-seq确定差异血液基因表达（n = 249）。糖尿病增加了结核病宿主转录组中基因表达变化的幅度，特别是显示出与先天性炎症相关的基因增加和适应性免疫应答减少。引人注目的是，患有IH和TB的患者表现出与患有糖尿病-TB的患者比仅患有TB的患者更相似的血液转录组。相对于单纯TB患者，糖尿病-TB和IH-TB患者的I型干扰素应答均降低。在患有TB和糖尿病的个体中的共病与改变的转录组相关，在这两种情况下预期炎症增强，但在共病患者中I型干扰素应答也减少，这表明TB转录组表型的意外解偶联。这些免疫功能障碍也存在于患有IH的个体中，这表明该群体也可能存在对结核病的免疫力改变。诊断为结核病的IH患者的结核病结局应进一步研究。我们的研究表明，糖尿病和结核病患者与单纯结核病患者相比，外周免疫谱发生了改变，这些差异也存在于中度高血糖患者中。
People with diabetes have an increased risk of developing active tuberculosis (TB) and are more likely to have poor TB-treatment outcomes, which may impact on control of TB as the prevalence of diabetes is increasing worldwide. Blood transcriptomes are altered in patients with active TB relative to healthy individuals. The effects of diabetes and intermediate hyperglycemia (IH) on this transcriptomic signature were investigated to enhance understanding of immunological susceptibility in diabetes-TB comorbidity. Whole blood samples were collected from active TB patients with diabetes (glycated hemoglobin [HbA1c] ≥6.5%) or IH (HbA1c = 5.7% to <6.5%), TB-only patients, and healthy controls in 4 countries: South Africa, Romania, Indonesia, and Peru. Differential blood gene expression was determined by RNA-seq (n = 249). Diabetes increased the magnitude of gene expression change in the host transcriptome in TB, notably showing an increase in genes associated with innate inflammatory and decrease in adaptive immune responses. Strikingly, patients with IH and TB exhibited blood transcriptomes much more similar to patients with diabetes-TB than to patients with only TB. Both diabetes-TB and IH-TB patients had a decreased type I interferon response relative to TB-only patients. Comorbidity in individuals with both TB and diabetes is associated with altered transcriptomes, with an expected enhanced inflammation in the presence of both conditions, but also reduced type I interferon responses in comorbid patients, suggesting an unexpected uncoupling of the TB transcriptome phenotype. These immunological dysfunctions are also present in individuals with IH, showing that altered immunity to TB may also be present in this group. The TB disease outcomes in individuals with IH diagnosed with TB should be investigated further. Our study shows that people with diabetes and tuberculosis have altered peripheral immune profiles compared to people with only tuberculosis, and that these differences also exist in patients with intermediate hyperglycemia.
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影响因子：
16.2
作者：
American Diabetes Association
通讯作者：
American Diabetes Association
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O'Garra A
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3.7
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Babu S
影响因子：
3.8
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