Engelhardt Institute of Molecular Biology, Russian Academy of Sciences, Moscow, Russia.
Belozersky Institute of Physico-Chemical Biology, Lomonosov Moscow State University, Moscow, Russia.
Front Immunol. 2023 Apr 19;14:1172467. doi: 10.3389/fimmu.2023.1172467. eCollection 2023.
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（NMR）是一种独特的长寿啮齿动物，对与年龄相关的疾病和癌症具有高度抗性。NMR 的免疫系统具有独特的细胞组成，其中髓样细胞较为常见。因此，详细评估 NMR 髓样细胞区室的表型和功能，可能揭示免疫调节和健康衰老的新机制。在这项研究中，我们检查了基因表达谱、活性氮物种和细胞因子产生以及经典（M1）和替代（M2）激活的 NMR 骨髓来源巨噬细胞（BMDM）的代谢活性。在促炎条件下，NMR 巨噬细胞的极化导致了预期的 M1 表型，其特征是促炎基因表达、细胞因子产生和有氧糖酵解增加，但同时伴随着一氧化氮（NO）产生减少。在全身 LPS 诱导的炎症条件下，NMR 血液单核细胞中也未检测到 NO 产生。总的来说，我们的结果表明，NMR 巨噬细胞能够在极化刺激下进行转录和代谢重编程，然而，与鼠类 M1 相比，NMR M1 具有特定的物种特征，表明 NMR 免疫系统存在独特的适应。
