Aquatic Environment and Health Management Division, ICAR-Central Institute of Fisheries Education, Panch Marg, Off Yari Road, Versova, Mumbai 400 061, India.
Aquatic Environment and Health Management Division, ICAR-Central Institute of Fisheries Education, Panch Marg, Off Yari Road, Versova, Mumbai 400 061, India.
Fish Shellfish Immunol. 2022 Dec;131:855-861. doi: 10.1016/j.fsi.2022.10.069. Epub 2022 Nov 3.
Trained immunity refers to the memory acquired by innate immune cells, leading to cross-protection and non-specific responses to subsequent infection, thereby improving host survival. Trained immunity induction is a combined effect of immune signaling, metabolic changes, and epigenetic modifications. The present study evaluated the induction of markers of the phenomenon of trained immunity in common carp, which is trained using β-glucan. The mammalian target of rapamycin (mtor) and hypoxia-inducible factor (hif1α), the metabolic basis of trained immunity; the histone deacetylase (hdac7), one of the markers of epigenetic modifications, metabolic activity of activated cells and expression profiles of proinflammatory cytokines viz. il6a, tnfαa2, and ifnγ were targeted in the study and analyzed in vivo. Besides in vivo analysis, in vitro analysis of mtorc2, hif1α, hdac7, and ifnγ were analyzed. In vitro analyses were performed on head kidney macrophages isolated and maintained in L-15 media and double trained with β-glucan at 100μg/mL. The culture supernatant was collected at different time intervals and processed for expression studies. Healthy common carp were injected with β-glucan at 20 mg/kg body weight for training followed by a resting phase for 6 days and were restimulated with the same dose. Head kidney was collected from the fish post-induction as well as post-restimulation. The expression profile of mtorc2, hdac7, and hif1α were found elevated post-stimulation of β-glucan. Further, a significantly upregulated expression profile of proinflammatory cytokines (ifnγ, il6a and tnfαa2) was observed. Increased glycolysis in the cells post-β-glucan stimulation was confirmed by the high lactate and LDH production detected in the cell culture supernatant. Overall, the study revealed the expression profile of the trained immunity markers and the increased metabolic activity in cells induced with β-glucan, which further validates that the action of trained immunity is indispensable in fish on encounter with a potential ligand. The study supports the existing reports on trained immunity in teleost fish with evidence at the genomic level. However, further studies are required to understand the responses and actions of trained immune cells during infection in detail.
训练免疫是指先天免疫细胞获得的记忆，导致对随后感染的交叉保护和非特异性反应，从而提高宿主的存活率。训练免疫的诱导是免疫信号、代谢变化和表观遗传修饰的综合作用。本研究评估了用β-葡聚糖对鲤鱼进行训练免疫诱导标记物的研究。哺乳动物雷帕霉素靶蛋白（mTOR）和低氧诱导因子（HIF1α）是训练免疫的代谢基础；组蛋白去乙酰化酶（HDAC7）是表观遗传修饰的标记物之一，细胞代谢活性和促炎细胞因子的表达谱，如 IL6A、TNFαA2 和 IFNγ，在体内进行了研究和分析。除了体内分析外，还对 mTORC2、HIF1α、HDAC7 和 IFNγ 进行了体外分析。体外分析是在分离并在 L-15 培养基中维持的头肾巨噬细胞上进行的，并在 100μg/ml 的β-葡聚糖下进行双重训练。在不同时间间隔收集培养上清液并进行表达研究。健康的鲤鱼用 20mg/kg 体重的β-葡聚糖注射进行训练，然后休息 6 天，用相同剂量再次刺激。在诱导后和再刺激后从鱼中收集头肾。发现 mTORC2、HDAC7 和 HIF1α 的表达谱在β-葡聚糖刺激后升高。此外，还观察到促炎细胞因子（IFNγ、IL6A 和 TNFαA2）的表达谱显著上调。通过检测细胞培养上清液中高乳酸和 LDH 的产生，证实了β-葡聚糖刺激后细胞内糖酵解的增加。总的来说，该研究揭示了用β-葡聚糖诱导的训练免疫标记物的表达谱和细胞代谢活性的增加，进一步证实了在鱼类遇到潜在配体时，训练免疫的作用是必不可少的。该研究支持在硬骨鱼类中关于训练免疫的现有报道，并提供了基因组水平的证据。然而，需要进一步的研究来详细了解感染期间训练免疫细胞的反应和作用。
