The emerging role of ASC in dendritic cell metabolism during Chlamydia infection.
The emerging role of ASC in dendritic cell metabolism during Chlamydia infection.
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DOI：
10.1371/journal.pone.0188643
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发表时间：
2017
期刊：
影响因子：
3.7
通讯作者：
He Q
中科院分区：
文献类型：
--
作者：
McKeithen DN;Omosun YO;Ryans K;Mu J;Xie Z;Simoneaux T;Blas-Machado U;Eko FO;Black CM;Igietseme JU;He Q
沙眼衣原体是一种在世界范围内引起性传播感染的细菌。树突状细胞（DCs）的调节功能在抗衣原体感染的保护性免疫中起重要作用。在此，我们研究了ASC在DCs代谢中的作用以及衣原体感染过程中DCs活化和功能的调节。在衣原体刺激后，与野生型（WT）DC相比，ASC-/-DC的成熟和抗原呈递功能受损，此外，ASC缺陷诱导衣原体刺激的DC的耐受表型。使用实时细胞外流量分析，我们表明，衣原体刺激的WT DC中的激活与代谢变化相关，其中线粒体氧化磷酸化（OXPHOS）被抑制，并且细胞致力于通过有氧糖酵解利用葡萄糖用于分化和抗原呈递功能。然而，在ASC-/-DC衣原体诱导的代谢变化被阻止，线粒体形态有显着的影响。衣原体刺激的ASC-/-DC的线粒体与刺激的WT DC中发现的正常狭窄的多形性嵴相比，嵴被破坏。总之，我们的研究结果表明，衣原体介导的激活的DC与代谢的转变，其中OXPHOS被抑制，从而致力于有氧糖酵解的DC，而ASC缺陷通过抑制线粒体内的DC代谢的重编程，从糖酵解到电子传递链，破坏DC的功能。
Chlamydia trachomatis is a bacterial agent that causes sexually transmitted infections worldwide. The regulatory functions of dendritic cells (DCs) play a major role in protective immunity against Chlamydia infections. Here, we investigated the role of ASC in DCs metabolism and the regulation of DCs activation and function during Chlamydia infection. Following Chlamydia stimulation, maturation and antigen presenting functions were impaired in ASC-/- DCs compared to wild type (WT) DCs, in addition, ASC deficiency induced a tolerant phenotype in Chlamydia stimulated DCs. Using real-time extracellular flux analysis, we showed that activation in Chlamydia stimulated WT DCs is associated with a metabolic change in which mitochondrial oxidative phosphorylation (OXPHOS) is inhibited and the cells become committed to utilizing glucose through aerobic glycolysis for differentiation and antigen presenting functions. However, in ASC-/- DCs Chlamydia-induced metabolic change was prevented and there was a significant effect on mitochondrial morphology. The mitochondria of Chlamydia stimulated ASC-/- DCs had disrupted cristae compared to the normal narrow pleomorphic cristae found in stimulated WT DCs. In conclusion, our results suggest that Chlamydia-mediated activation of DCs is associated with a metabolic transition in which OXPHOS is inhibited, thereby dedicating the DCs to aerobic glycolysis, while ASC deficiency disrupts DCs function by inhibiting the reprogramming of DCs metabolism within the mitochondria, from glycolysis to electron transport chain.
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