Jiangsu Key Laboratory of Immunity and Metabolism, Department of Pathogen Biology and Immunology, Xuzhou Medical University, Xuzhou, 221004, Jiangsu Province, China.
JOINN Laboratories (Suzhou), Suzhou, 215421, Jiangsu Province, China.
Inflammation. 2020 Aug;43(4):1323-1336. doi: 10.1007/s10753-020-01211-2.
Trained immunity has been recently identified in innate immune cells, which undergo long-term epigenetic and metabolic reprogramming after exposure to pathogens for protection from secondary infections. (1, 3)/(1, 6)-β-glucan derived from fungi can induce potent trained immunity; however, the effect of (1, 3)/(1, 4)-β-glucan (rich in dietary fiber oat) on trained immunity has not been reported. In the present study, two cell culture systems for trained immunity induction were validated in monocytes/macrophages from mouse bone myeloid and human THP-1 cells exposed to positive inducers of trained immunity, including β-glucan from Trametes versicolor or human-oxidized low-density lipoprotein. Primed with oat β-glucan, the mRNA expression and production of TNF-α and IL-6 significantly increased in response to re-stimulation of TLR-4/2 ligands. Moreover, the expression of several key enzymes in glycolytic pathway and tricarboxylic acid cycle was significantly upregulated. In addition, inhibiting these enzymes decreased the production of TNF-α and IL-6 boosted by oat β-glucan. These results show that oat β-glucan induces trained immunity through metabolic reprogramming. This provides important evidence that dietary fiber can maintain the long-term responsiveness of the innate immune system, which may benefit for prevention of infectious diseases or cancers.
训练免疫最近在先天免疫细胞中被发现,这些细胞在接触病原体后会经历长期的表观遗传和代谢重编程,以防止二次感染。(1,3)/(1,6)-β-葡聚糖来源于真菌,可以诱导强烈的训练免疫;然而,(1,3)/(1,4)-β-葡聚糖(富含膳食纤维的燕麦)对训练免疫的影响尚未报道。在本研究中,两种用于诱导训练免疫的细胞培养系统在来自小鼠骨髓髓系的单核细胞/巨噬细胞和人 THP-1 细胞中得到了验证,这些细胞暴露于训练免疫的阳性诱导剂中,包括云芝β-葡聚糖或人氧化低密度脂蛋白。用燕麦β-葡聚糖预先处理后,TNF-α 和 IL-6 的 mRNA 表达和产生在 TLR-4/2 配体再次刺激时显著增加。此外,糖酵解途径和三羧酸循环中的几个关键酶的表达也显著上调。此外,抑制这些酶的活性会降低由燕麦β-葡聚糖增强的 TNF-α 和 IL-6 的产生。这些结果表明,燕麦β-葡聚糖通过代谢重编程诱导训练免疫。这为膳食纤维可以维持先天免疫系统的长期反应性提供了重要证据,这可能有益于预防传染病或癌症。