Table_2_Macrophages from naked mole-rat possess distinct immunometabolic signatures upon polarization.xlsx

The naked mole-rat (NMR) is a unique long-lived rodent which is highly resistant to age-associated disorders and cancer. The immune system of NMR possesses a distinct cellular composition with the prevalence of myeloid cells. Thus, the detailed phenotypical and functional assessment of NMR myeloid cell compartment may uncover novel mechanisms of immunoregulation and healthy aging. In this study gene expression signatures, reactive nitrogen species and cytokine production, as well as metabolic activity of classically (M1) and alternatively (M2) activated NMR bone marrow-derived macrophages (BMDM) were examined. Polarization of NMR macrophages under pro-inflammatory conditions led to expected M1 phenotype characterized by increased pro-inflammatory gene expression, cytokine production and aerobic glycolysis, but paralleled by reduced production of nitric oxide (NO). Under systemic LPS-induced inflammatory conditions NO production also was not detected in NMR blood monocytes. Altogether, our results indicate that NMR macrophages are capable of transcriptional and metabolic reprogramming under polarizing stimuli, however, NMR M1 possesses species-specific signatures as compared to murine M1, implicating distinct adaptations in NMR immune system.

裸鼹鼠（naked mole-rat, NMR）是一种独特的长寿啮齿类动物，对年龄相关疾病与癌症具有极强抗性。其免疫系统拥有独特的细胞组成，髓系细胞（myeloid cells）占比极高。因此，对裸鼹鼠髓系细胞区室进行全面的表型与功能评估，或可揭示免疫调控与健康衰老的全新机制。本研究针对经典活化（M1）与替代活化（M2）状态下的裸鼹鼠骨髓来源巨噬细胞（bone marrow-derived macrophages, BMDM）的基因表达特征、活性氮物种（reactive nitrogen species）生成、细胞因子（cytokine）分泌以及代谢活性开展了检测分析。在促炎条件下诱导裸鼹鼠巨噬细胞极化为预期的M1表型，该表型以促炎基因表达上调、细胞因子分泌增加与有氧糖酵解增强为特征，但与此同时一氧化氮（nitric oxide, NO）的生成量却有所降低。在全身性脂多糖（lipopolysaccharide, LPS）诱导的炎症状态下，裸鼹鼠血液单核细胞同样未检测到NO的生成。综上，本研究结果显示，裸鼹鼠巨噬细胞可在极化刺激下完成转录与代谢重编程；但相较于小鼠M1巨噬细胞，裸鼹鼠M1巨噬细胞具有物种特异性的表达特征，这表明裸鼹鼠的免疫系统存在独特的适应性机制。