Human monocyte-derived macrophage responses to M. tuberculosis differ by the host's tuberculosis, diabetes or obesity status, and are enhanced by rapamycin.
Human monocyte-derived macrophage responses to M. tuberculosis differ by the host's tuberculosis, diabetes or obesity status, and are enhanced by rapamycin.
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DOI：
10.1016/j.tube.2020.102047
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发表时间：
2021-01
期刊：
影响因子：
--
通讯作者：
Jagannath C
中科院分区：
文献类型：
--
作者：
Restrepo BI;Khan A;Singh VK;Erica de-Leon;Aguillón-Durán GP;Ledezma-Campos E;Canaday DH;Jagannath C
人类巨噬细胞在控制结核病（TB）方面发挥着重要作用，但其抗分枝杆菌机制在代谢改变的个体中仍不清楚，如肥胖（TB保护）或糖尿病（TB风险）。为了帮助辨别这一点，我们的目标是：i）评估宿主的TB状态或其共病对其单核细胞衍生的巨噬细胞（MDM）的抗分枝杆菌应答的影响，以及ii）确定自噬诱导剂雷帕霉素是否可以增强这些应答。我们使用来自新诊断的结核病患者、其密切接触者和未暴露对照的MDM。来自TB患者的MDM活化T细胞（抗原呈递的替代物）或杀死M的能力降低。结核病（Mtb）与非结核病对照相比。来自肥胖参与者的MDM具有较高的抗原呈递能力，而来自慢性糖尿病患者的MDM显示出较低的Mtb杀伤力。用雷帕霉素激活MDM导致增强的抗分枝杆菌活性，而与TB状态无关，但在糖尿病患者中不那么有效。需要使用来自有或没有代谢合并症的TB患者的MDM进行进一步研究，以：i）阐明宿主因素影响Mtb应答的机制，和ii）评估使用自噬诱导药物如雷帕霉素增强巨噬细胞功能的宿主定向治疗。
Human macrophages play a major role in controlling tuberculosis (TB), but their anti-mycobacterial mechanisms remain unclear among individuals with metabolic alterations like obesity (TB protective) or diabetes (TB risk). To help discern this, we aimed to: i) Evaluate the impact of the host’s TB status or their comorbidities on the anti-mycobacterial responses of their monocyte-derived macrophages (MDMs), and ii) determine if the autophagy inducer rapamycin, can enhance these responses. We used MDMs from newly diagnosed TB patients, their close contacts and unexposed controls. The MDMs from TB patients had a reduced capacity to activate T cells (surrogate for antigen presentation) or kill M. tuberculosis (Mtb) when compared to non-TB controls. The MDMs from obese participants had a higher antigen presenting capacity, whereas those from chronic diabetes patients displayed lower Mtb killing. The activation of MDMs with rapamycin led to an enhanced anti-mycobacterial activity irrespective of TB status but was not as effective in patients with diabetes. Further studies are warranted using MDMs from TB patients with or without metabolic comorbidities to: i) elucidate the mechanisms through which host factors affect Mtb responses, and ii) evaluate host directed therapy using autophagy-inducing drugs like rapamycin to enhance macrophage function.
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结核分枝杆菌免疫逃避的机制是对结核病疫苗设计的挑战。
影响因子：
30.3
作者：
Ernst JD
通讯作者：
Ernst JD
DOI：
10.2471/blt.10.085738
发表时间：
2011-05-01
期刊：
Bulletin of the World Health Organization: International Journal of Public Health
影响因子：
--
作者：
Restrepo, Blanca I;Camerlin, Aulasa J;Fisher-Hoch, Susan P
通讯作者：
Fisher-Hoch, Susan P
影响因子：
4.4
作者：
Kusner, DJ;Barton, JA
通讯作者：
Barton, JA
影响因子：
2.4
作者：
Lee, Ye-Jin;Han, Sung Koo;Heo, Eun Young
通讯作者：
Heo, Eun Young
DOI：
10.1084/jem.20172020
发表时间：
2018-04-02
期刊：
The Journal of experimental medicine
影响因子：
--
作者：
Huang L;Nazarova EV;Tan S;Liu Y;Russell DG
通讯作者：
Russell DG