Failure to decrease HbA1c levels following TB treatment is associated with elevated Th1/Th17 CD4+ responses.
Failure to decrease HbA1c levels following TB treatment is associated with elevated Th1/Th17 CD4+ responses.
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DOI：
10.3389/fimmu.2023.1151528
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发表时间：
2023
影响因子：
7.3
通讯作者：
中科院分区：
文献类型：
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全球代谢性疾病负担的不断增加影响了许多地区对地方性结核病的控制，因为糖尿病患者发生活动性结核病的可能性是非糖尿病患者的三倍。活动性结核病还可在急性感染期间和长期内促进葡萄糖耐受不良，这可能是由免疫反应的各个方面驱动的。识别结核病治疗后可能出现持续性高血糖的患者，将有助于更密切地监测和护理，并提高对潜在免疫代谢失调的理解。在南非德班的一项前瞻性观察队列研究中，我们测量了血浆细胞因子水平、T细胞表型和功能反应与肺结核治疗前后血红蛋白A1c （HbA1c）变化的关系。从治疗开始到12个月的随访，根据HbA1c稳定/升高（n = 16）和HbA1c下降（n = 46）水平对参与者进行分层。在结核病治疗期间，HbA1c保持稳定/升高的个体血浆中CD62 p-选择素升高（1.5倍），IL-10下调（0.85倍）。这伴随着促炎结核特异性IL-17产生（Th17）的增加。此外，该组的Th1反应上调，包括TNF-α产生和CX3CR1表达，IL-4和IL-13产生降低。最后，TNF-α+ IFNγ+ CD8+ T细胞与HbA1c稳定/升高相关。与HbA1c降低组相比，HbA1c稳定/升高组的这些变化都有显著差异。总的来说，这些数据表明HbA1c稳定/升高的患者具有升高的促炎状态。结核病治疗后未解决的血糖异常患者的持续炎症和T细胞活性升高可能表明感染未能完全解决或可能促进这些患者的持续血糖异常，需要进一步的研究来探索潜在的机制。
The rising global burden of metabolic disease impacts the control of endemic tuberculosis (TB) in many regions, as persons with diabetes mellitus (DM) are up to three times more likely to develop active TB than those without DM. Active TB can also promote glucose intolerance during both acute infection and over a longer term, potentially driven by aspects of the immune response. Identifying patients likely to have persistent hyperglycemia following TB treatment would enable closer monitoring and care, and an improved understanding of underlying immunometabolic dysregulation. We measured the relationship of plasma cytokine levels, T cell phenotypes and functional responses with the change in hemoglobin A1c (HbA1c) before and after treatment of pulmonary TB in a prospective observational cohort in Durban, South Africa. Participants were stratified based on stable/increased HbA1c (n = 16) versus decreased HbA1c (n = 46) levels from treatment initiation to 12 month follow-up. CD62 P-selectin was up- (1.5-fold) and IL-10 downregulated (0.85-fold) in plasma among individuals whose HbA1c remained stable/increased during TB treatment. This was accompanied by increased pro-inflammatory TB-specific IL-17 production (Th17). In addition, Th1 responses were upregulated in this group, including TNF-α production and CX3CR1 expression, with decreased IL-4 and IL-13 production. Finally, the TNF-α+ IFNγ+ CD8+ T cells were associated with stable/increased HbA1c. These changes were all significantly different in the stable/increased HbA1c relative to the decreased HbA1c group. Overall, these data suggest that patients with stable/increased HbA1c had an increased pro-inflammatory state. Persistent inflammation and elevated T cell activity in individuals with unresolved dysglycemia following TB treatment may indicate failure to fully resolve infection or may promote persistent dysglycemia in these individuals, and further studies are needed to explore potential mechanisms.
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影响因子：
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