Africa Health Research Institute, University of KwaZulu-Natal, Durban, South Africa.
Vanderbilt Tuberculosis Center, Vanderbilt University School of Medicine, Nashville, TN, United States.
Front Immunol. 2024 Nov 13;15:1465448. doi: 10.3389/fimmu.2024.1465448. eCollection 2024.
The impact of human pulmonary tuberculosis (TB) on the bioenergetic metabolism of circulating immune cells remains elusive, as does the resolution of these effects with TB treatment. In this study, the rates of oxidative phosphorylation (OXPHOS) and glycolysis in circulating lymphocytes and monocytes of patients with drug-susceptible TB at diagnosis, 2 months, and 6 months during treatment, and 12 months after diagnosis were investigated using extracellular flux analysis. At diagnosis, the bioenergetic parameters of both blood lymphocytes and monocytes of TB patients were severely impaired in comparison to non-TB and non-HIV-infected controls. However, most bioenergetic parameters were not affected by HIV status or glycemic index. Treatment of TB patients restored the % spare respiratory capacity (%SRC) of the circulating lymphocytes to that observed in non-TB and non-HIV infected controls by 12 months. Treatment also improved the maximal respiration of circulating lymphocytes and the %SRC of circulating monocytes of the TB patients. Notably, the differential correlation of the clinical and bioenergetic parameters of the monocytes and lymphocytes from the controls and TB patients at baseline and month 12 was consistent with improved metabolic health and resolution of inflammation following successful TB treatment. Network analysis of the bioenergetic parameters of circulating immune cells with serum cytokine levels indicated a highly coordinated immune response at month 6. These findings underscore the importance of metabolic health in combating TB, supporting the need for further investigation of the bioenergetic immunometabolism associated with TB infection for novel therapeutic approaches aimed at bolstering cellular energetics to enhance immune responses and expedite recovery in TB patients.
人类肺结核（TB）对循环免疫细胞的生物能量代谢的影响仍不清楚，TB 治疗后这些影响的解决情况也是如此。在这项研究中，使用细胞外通量分析研究了初诊时、治疗 2 个月和 6 个月以及诊断后 12 个月时耐多药 TB 患者循环淋巴细胞和单核细胞的氧化磷酸化（OXPHOS）和糖酵解率。与非 TB 和非 HIV 感染对照者相比，初诊时 TB 患者的血液淋巴细胞和单核细胞的生物能量参数均严重受损。然而，大多数生物能量参数不受 HIV 状态或血糖指数的影响。TB 患者的治疗将循环淋巴细胞的备用呼吸能力（%SRC）恢复到 12 个月时非 TB 和非 HIV 感染对照者的水平。治疗还改善了循环淋巴细胞的最大呼吸和循环单核细胞的%SRC。值得注意的是，对照组和 TB 患者的单核细胞和淋巴细胞的临床和生物能量参数在基线和 12 个月时的差异相关性与成功治疗 TB 后代谢健康的改善和炎症的消退一致。循环免疫细胞的生物能量参数与血清细胞因子水平的网络分析表明，在 6 个月时有一个高度协调的免疫反应。这些发现强调了代谢健康在对抗 TB 中的重要性，支持进一步研究与 TB 感染相关的生物能量免疫代谢，以寻找新的治疗方法，增强细胞能量以增强免疫反应并加速 TB 患者的康复。
