克罗地亚里耶卡大学Bojan Poli团队近期取得重要工作进展，他们研究提出，IFNγ依赖性免疫-内分泌回路降低血糖以增强先天性抗病毒免疫反应。相关研究成果2024年5月29日在线发表于《自然—免疫学》杂志上。

据介绍，病毒感染会使人们感到恶心，因为免疫系统会改变系统代谢以更好地对抗病原体。这些变化的程度与疾病的严重程度有关。血糖是否受到感染诱导的调节大多是未知的。

研究人员发现强烈的非致命性感染限制了全身葡萄糖的可用性，这促进了抗病毒的I型干扰素（IFN-I）反应。病毒感染后，研究人员发现γδ T细胞产生的IFNγ刺激胰腺β细胞增加葡萄糖诱导的胰岛素释放。随后，高胰岛素血症降低了肝脏葡萄糖输出。葡萄糖限制通过减少乳酸介导的对IRF3和NF-κB信号传导的抑制来增强IFN-I的产生。诱导的高血糖抑制了IFN-I的产生，并增加了感染后的死亡率。

总之，这一研究结果表明，葡萄糖限制是一种使身体对病毒病原体反应增强的生理机制。这种免疫-内分泌回路在高血糖中被破坏，这可能解释了为什么糖尿病患者更容易受到病毒感染。

附：英文原文

Title: An IFNγ-dependent immune–endocrine circuit lowers blood glucose to potentiate the innate antiviral immune response

Author: estan, Marko, Mikainovi, Sanja, Beni, Ante, Wueest, Stephan, Dimitropoulos, Christoforos, Mladeni, Karlo, Krapi, Mia, Hirl, Lea, Glantzspiegel, Yossef, Rasteiro, Ana, Aliseychik, Maria, Cekinovi Grbea, urica, Turk Wensveen, Tamara, Babi, Marina, Gat-Viks, Irit, Veiga-Fernandes, Henrique, Konrad, Daniel, Wensveen, Felix M., Poli, Bojan

Issue&Volume: 2024-05-29

Abstract: Viral infection makes us feel sick as the immune system alters systemic metabolism to better fight the pathogen. The extent of these changes is relative to the severity of disease. Whether blood glucose is subject to infection-induced modulation is mostly unknown. Here we show that strong, nonlethal infection restricts systemic glucose availability, which promotes the antiviral type I interferon (IFN-I) response. Following viral infection, we find that IFNγ produced by γδ T cells stimulates pancreatic β cells to increase glucose-induced insulin release. Subsequently, hyperinsulinemia lessens hepatic glucose output. Glucose restriction enhances IFN-I production by curtailing lactate-mediated inhibition of IRF3 and NF-κB signaling. Induced hyperglycemia constrained IFN-I production and increased mortality upon infection. Our findings identify glucose restriction as a physiological mechanism to bring the body into a heightened state of responsiveness to viral pathogens. This immune–endocrine circuit is disrupted in hyperglycemia, possibly explaining why patients with diabetes are more susceptible to viral infection.

DOI: 10.1038/s41590-024-01848-3

Source: https://www.nature.com/articles/s41590-024-01848-3