Department Microbiology, Biochemistry, and, Immunology, Morehouse School of Medicine, Atlanta, GA, United States of America.
Department of Biology, Clark Atlanta University, Atlanta, GA, United States of America.
PLoS One. 2017 Dec 7;12(12):e0188643. doi: 10.1371/journal.pone.0188643. eCollection 2017.
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.
沙眼衣原体是一种导致全球性传播感染的细菌病原体。树突状细胞（DCs）的调节功能在针对衣原体感染的保护性免疫中起着重要作用。在这里，我们研究了 ASC 在 DCs 代谢中的作用，以及在衣原体感染期间对 DCs 激活和功能的调节作用。与野生型（WT）DCs 相比，在衣原体刺激后，ASC-/-DCs 的成熟和抗原呈递功能受损，此外，ASC 缺陷在衣原体刺激的 DCs 中诱导了耐受表型。通过实时细胞外通量分析，我们表明，WT DCs 中衣原体刺激的激活与代谢变化相关，其中线粒体氧化磷酸化（OXPHOS）受到抑制，细胞通过有氧糖酵解为分化和抗原呈递功能而转向利用葡萄糖。然而，在 ASC-/-DCs 中，衣原体诱导的代谢变化被阻止，并且对线粒体形态有显著影响。与在刺激的 WT DCs 中发现的正常狭窄多形嵴相比，衣原体刺激的 ASC-/-DCs 的线粒体嵴结构被破坏。总之，我们的结果表明，衣原体介导的 DCs 激活与 OXPHOS 受到抑制的代谢转变有关，从而使 DCs专注于有氧糖酵解，而 ASC 缺陷通过抑制线粒体中 DCs 代谢的重编程（从糖酵解到电子传递链）来破坏 DCs 的功能。
