Garcia-Valtanen Pablo, Guzman-Genuino Ruth Marian, Williams David L, Hayball John D, Diener Kerrilyn R
Experimental Therapeutics Laboratory, Hanson and Sansom Institute for Health Research, School of Pharmacy and Medical Science, University of South Australia, Adelaide, SA, Australia.
Department of Surgery, Center of Excellence in Inflammation, Infectious Disease and Immunity, Quillen College of Medicine, East Tennessee State University, Johnson City, TN, USA.
Immunol Cell Biol. 2017 Aug;95(7):601-610. doi: 10.1038/icb.2017.13. Epub 2017 Feb 23.
The β-1, 3 (d)-glucan (β-glucan) present in the cell wall of Candida albicans induces epigenetic changes in human monocytes resulting in primed macrophages exhibiting increased cytokine responsiveness to reinfection. This phenomenon is referred to as trained immunity or innate immune memory. However, whether β-glucan can reprogramme murine monocytes in vitro or induce lasting effects in vivo has yet to be elucidated. Thus, purified murine spleen-derived monocytes were primed with β-glucan in vitro and assessed for markers of differentiation and survival. Important macrophage cell markers during monocyte-to-macrophage differentiation were downregulated and survival enhanced due to partial inhibition of apoptosis. Increased survival and not the β-glucan training effect explained the elevated production of tumour necrosis factor-α (TNFα) and interleukin-6 (IL-6) induced by subsequent lipopolysaccharide (LPS) challenge. In vivo, 4 days after systemic administration of β-glucan, mice were more responsive to LPS challenge as shown by the increased serum levels of TNFα, IL-6 and IL-10, an effect shown to be short lived as enhanced cytokine production was lost by day 20. Here, we have characterised murine macrophages derived from β-glucan-primed monocytes based on their surface marker expression and for the first time provide evidence that the training effect of β-glucan in vivo declines within a 3-week period.
白色念珠菌细胞壁中的β-1, 3（d）-葡聚糖（β-葡聚糖）可诱导人类单核细胞发生表观遗传变化，从而使致敏巨噬细胞对再次感染表现出更高的细胞因子反应性。这种现象被称为训练免疫或先天免疫记忆。然而，β-葡聚糖是否能在体外对小鼠单核细胞进行重编程或在体内诱导持久效应，尚未得到阐明。因此，体外使用β-葡聚糖对纯化的小鼠脾脏来源的单核细胞进行致敏，并评估其分化和存活标志物。在单核细胞向巨噬细胞分化过程中，重要的巨噬细胞标志物表达下调，且由于细胞凋亡的部分抑制，细胞存活能力增强。存活能力的提高而非β-葡聚糖的训练效应解释了随后脂多糖（LPS）刺激诱导的肿瘤坏死因子-α（TNFα）和白细胞介素-6（IL-6）产量的升高。在体内，全身给予β-葡聚糖4天后，小鼠对LPS刺激的反应更强，表现为TNFα、IL-6和IL-10的血清水平升高，但这种效应是短暂的，因为到第20天时细胞因子产量的增加就消失了。在这里，我们根据表面标志物表达对源自β-葡聚糖致敏单核细胞的小鼠巨噬细胞进行了表征，并首次提供证据表明β-葡聚糖在体内的训练效应在3周内会下降。
