加拿大麦吉尔大学Maziar Divangahi、Nargis Khan研究团队发现，β-葡聚糖重编程中性粒细胞以促进其对甲型流感病毒的耐受性。2025年1月8日出版的《自然—免疫学》发表了这项成果。

据了解，对疾病产生耐受是一种进化保守的宿主防御策略，可在不影响病原体负荷的情况下保持组织完整性和生理机能。与宿主抗性不同，疾病耐受性的内在机制仍鲜为人知。

研究人员探讨了一种佐剂（β-葡聚糖）是否能重塑先天免疫，从而提供对甲型流感病毒（IAV）感染的保护。β-葡聚糖治疗可降低IAV感染的发病率和死亡率，与宿主抵抗力无关。肺组织通过RoRγt⁺ T细胞招募更多中性粒细胞以提高存活率。

β-葡聚糖处理能以1型干扰素依赖的方式促进粒细胞生成，从而产生一种独特的未成熟中性粒细胞亚群，这种亚群利用线粒体氧化代谢并产生白细胞介素-10。

总之，该研究数据表明，β-葡聚糖能重塑造血干细胞，使其生成具有新 “调节 ”功能的中性粒细胞，而这种功能是促进疾病耐受性，和维持肺组织完整性以抵御病毒感染所必需的。

附：英文原文

Title: β-Glucan reprograms neutrophils to promote disease tolerance against influenza A virus

Author: Khan, Nargis, Tran, Kim A., Chevre, Raphael, Locher, Veronica, Richter, Mathis, Sun, Sarah, Sadeghi, Mina, Pernet, Erwan, Herrero-Cervera, Andrea, Grant, Alexandre, Saif, Ahmed, Downey, Jeffrey, Kaufmann, Eva, Khader, Shabaana Abdul, Joubert, Philippe, Barreiro, Luis B., Yipp, Bryan G., Soehnlein, Oliver, Divangahi, Maziar

Issue&Volume: 2025-01-08

Abstract: Disease tolerance is an evolutionarily conserved host defense strategy that preserves tissue integrity and physiology without affecting pathogen load. Unlike host resistance, the mechanisms underlying disease tolerance remain poorly understood. In the present study, we investigated whether an adjuvant (β-glucan) can reprogram innate immunity to provide protection against influenza A virus (IAV) infection. β-Glucan treatment reduces the morbidity and mortality against IAV infection, independent of host resistance. The enhanced survival is the result of increased recruitment of neutrophils via RoRγt+ T cells in the lung tissue. β-Glucan treatment promotes granulopoiesis in a type 1 interferon-dependent manner that leads to the generation of a unique subset of immature neutrophils utilizing a mitochondrial oxidative metabolism and producing interleukin-10. Collectively, our data indicate that β-glucan reprograms hematopoietic stem cells to generate neutrophils with a new ‘regulatory’ function, which is required for promoting disease tolerance and maintaining lung tissue integrity against viral infection.

DOI: 10.1038/s41590-024-02041-2

Source: https://www.nature.com/articles/s41590-024-02041-2