Formation of Foamy Macrophages by Tuberculous Pleural Effusions Is Triggered by the Interleukin-10/Signal Transducer and Activator of Transcription 3 Axis through ACAT Upregulation.
Formation of Foamy Macrophages by Tuberculous Pleural Effusions Is Triggered by the Interleukin-10/Signal Transducer and Activator of Transcription 3 Axis through ACAT Upregulation.
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DOI：
10.3389/fimmu.2018.00459
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发表时间：
2018
影响因子：
7.3
通讯作者：
Balboa L
中科院分区：
文献类型：
--
作者：
Genoula M;Marín Franco JL;Dupont M;Kviatcovsky D;Milillo A;Schierloh P;Moraña EJ;Poggi S;Palmero D;Mata-Espinosa D;González-Domínguez E;León Contreras JC;Barrionuevo P;Rearte B;Córdoba Moreno MO;Fontanals A;Crotta Asis A;Gago G;Cougoule C;Neyrolles O;Maridonneau-Parini I;Sánchez-Torres C;Hernández-Pando R;Vérollet C;Lugo-Villarino G;Sasiain MDC;Balboa L
结核分枝杆菌 (Mtb) 在人类宿主体内持续存在的能力依赖于多种免疫逃避策略，例如导致泡沫巨噬细胞 (FM) 形成的脂质代谢失调。然而，导致 Mtb 感染的巨噬细胞出现泡沫表型的具体宿主因素仍然未知。在此，我们的目的是解决在 Mtb 感染的情况下宿主细胞因子是否有助于 FM 形成。我们的方法基于使用结核性胸腔积液（TB-PE）的无细胞部分作为结核分枝杆菌感染期间释放的局部因子的生理来源。我们发现，通过脂质体、细胞内胆固醇和清道夫受体 CD36 以及酰基辅酶 A：胆固醇酰基转移酶 (ACAT) 表达的增加观察到 TB-PE 诱导 FM 分化。重要的是，TB-PE 导致的白细胞介素 10 (IL-10) 消耗阻止了所有这些参数的增加。此外，我们观察到结核病患者胸膜细胞中 IL-10 水平与载脂 CD14+ 细胞数量呈正相关，表明 FM 分化发生在胸膜环境内。在IL-10信号下游，我们注意到转录因子信号转导子和转录激活子3被TB-PE激活，其化学抑制作用阻止了巨噬细胞中脂质体的积累和ACAT的表达。在宿主免疫反应方面，TB-PE处理的巨噬细胞表现出免疫抑制特性并承担更高的细菌负荷。最后，我们使用来自 IL-10−/− 小鼠的骨髓源性巨噬细胞证实了我们的结果，表明 IL-10 缺乏部分阻止了 Mtb 脂质暴露后泡沫表型的诱导。总之，我们的结果证明了 IL-10 在 Mtb 感染情况下促进 FM 分化的作用，有助于我们了解宿主代谢因素的改变如何有利于病原体的持久存在。
The ability of Mycobacterium tuberculosis (Mtb) to persist in its human host relies on numerous immune evasion strategies, such as the deregulation of the lipid metabolism leading to the formation of foamy macrophages (FM). Yet, the specific host factors leading to the foamy phenotype of Mtb-infected macrophages remain unknown. Herein, we aimed to address whether host cytokines contribute to FM formation in the context of Mtb infection. Our approach is based on the use of an acellular fraction of tuberculous pleural effusions (TB-PE) as a physiological source of local factors released during Mtb infection. We found that TB-PE induced FM differentiation as observed by the increase in lipid bodies, intracellular cholesterol, and expression of the scavenger receptor CD36, as well as the enzyme acyl CoA:cholesterol acyl transferase (ACAT). Importantly, interleukin-10 (IL-10) depletion from TB-PE prevented the augmentation of all these parameters. Moreover, we observed a positive correlation between the levels of IL-10 and the number of lipid-laden CD14+ cells among the pleural cells in TB patients, demonstrating that FM differentiation occurs within the pleural environment. Downstream of IL-10 signaling, we noticed that the transcription factor signal transducer and activator of transcription 3 was activated by TB-PE, and its chemical inhibition prevented the accumulation of lipid bodies and ACAT expression in macrophages. In terms of the host immune response, TB-PE-treated macrophages displayed immunosuppressive properties and bore higher bacillary loads. Finally, we confirmed our results using bone marrow-derived macrophage from IL-10−/− mice demonstrating that IL-10 deficiency partially prevented foamy phenotype induction after Mtb lipids exposure. In conclusion, our results evidence a role of IL-10 in promoting the differentiation of FM in the context of Mtb infection, contributing to our understanding of how alterations of the host metabolic factors may favor pathogen persistence.
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DOI：
10.1007/5584_2014_105
发表时间：
2015-01-01
期刊：
RESPIRATORY CARCINOGENESIS
影响因子：
--
作者：
Klimiuk, J.;Krenke, R.;Chazan, R.
通讯作者：
Chazan, R.
体重指数和结核病和死亡的风险。
DOI：
10.1097/qad.0b013e32833a2a4a
发表时间：
2010-06-19
期刊：
AIDS (London, England)
影响因子：
--
作者：
Hanrahan CF;Golub JE;Mohapi L;Tshabangu N;Modisenyane T;Chaisson RE;Gray GE;McIntyre JA;Martinson NA
通讯作者：
Martinson NA
影响因子：
7.3
作者：
Ahluwalia PK;Pandey RK;Sehajpal PK;Prajapati VK
通讯作者：
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影响因子：
3.2
作者：
Hunter, Robert L.;Jagannath, Chinnaswamy;Actor, Jeffrey K.
通讯作者：
Actor, Jeffrey K.
影响因子：
28.2
作者：
Kumar, Nathella Pavan;Moideen, Kadar;Babu, Subash
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