Yang Wenxian, Li Li, Li Guanlin, Li Xiuhui, Liu Hongyan, Han Xuelian, Wang Yuan, Sun Yali, Wei Yuwei, Gao Bo, Zhao Guangyu, Sun Lei, Li Min
CAS Key Laboratory of Pathogenic Microbiology and Immunology, Institute of Microbiology, Chinese Academy of Sciences, Beijing 100101, China.
You'an Hospital, Capital Medical University, Beijing, Fengtai 100069, China.
iScience. 2024 Nov 15;27(12):111388. doi: 10.1016/j.isci.2024.111388. eCollection 2024 Dec 20.
Inflammatory cells infiltration in the cerebrospinal fluid is a hallmark of severe enterovirus 71 (EV71) infection, but which type of immune cells are critical for severe EV71 infection remains unclear. Here, we observe that both neutrophils and macrophages are increased in the brains of patients and mice with severe EV71 infection, and the depletion of neutrophils but not macrophages results in a marked enhancement of survival of EV71-infected mice. Furthermore, CCR1/3 may play an important role in CCL3 facilitating the accumulation of neutrophils in the brains of patients. Inhibition of CCL3 by anti-CCL3 antibodies or selected miRNAs significantly reduces the neutrophils infiltration in brains and the mortality of EV71-infected mice. Collectively, CCL3-mediated neutrophils recruitment into the brain contributes to the severe immunopathology of EV71 infection, which provides a potential diagnostic and therapeutic target for EV71 infection.
脑脊液中的炎性细胞浸润是重症肠道病毒71型（EV71）感染的一个标志，但对于重症EV71感染而言，哪种类型的免疫细胞至关重要仍不清楚。在此，我们观察到重症EV71感染的患者和小鼠脑内中性粒细胞和巨噬细胞均增多，而且去除中性粒细胞而非巨噬细胞可显著提高EV71感染小鼠的存活率。此外，CCR1/3可能在CCL3促进患者脑内中性粒细胞聚集过程中发挥重要作用。用抗CCL3抗体或特定的微小RNA抑制CCL3可显著减少脑内中性粒细胞浸润及EV71感染小鼠的死亡率。总体而言，CCL3介导的中性粒细胞向脑内募集促成了EV71感染的严重免疫病理学改变，这为EV71感染提供了一个潜在的诊断和治疗靶点。
