Table_1_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）是一类独特的长寿啮齿动物，对衰老相关病症与癌症具有高度抗性。其免疫系统拥有独特的细胞组成，髓系细胞占比颇高。因此，对裸鼹鼠髓系细胞区室进行详尽的表型与功能评估，或可揭示免疫调节与健康衰老的全新机制。本研究检测了经典激活（M1型）与替代激活（M2型）的裸鼹鼠骨髓来源巨噬细胞（bone marrow-derived macrophages, BMDM）的基因表达特征、活性氮物种生成、细胞因子产生情况以及代谢活性。在促炎条件下对裸鼹鼠巨噬细胞进行极化诱导，可得到预期的M1表型，其特征为促炎基因表达上调、细胞因子分泌增加以及有氧糖酵解增强，但同时伴随一氧化氮（nitric oxide, NO）生成量降低。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中同样未检测到一氧化氮的产生。综合所有实验结果，本研究表明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型巨噬细胞具有物种特异性的表达特征，这暗示裸鼹鼠免疫系统存在独特的适应性机制。