杜克-新加坡国立大学Ashley L. St. John小组发现，胎儿单核巨噬细胞在先天性感染过程中对寨卡病毒神经侵袭与神经保护的不同贡献。这一研究成果于2024年11月11日在线发表在国际学术期刊《细胞》上。
研究人员利用小鼠模型，识别了胎儿单核细胞/巨噬细胞类型和小胶质细胞，在寨卡病毒（ZIKV）传播与清除中的不同功能作用。ZIKV感染的原始巨噬细胞从卵黄囊的迁移，促进了初期的胎儿病毒接种，而招募的单核细胞则促进了非生产性的神经炎症。相反，驻留在大脑中的分化小胶质细胞具有保护作用，限制了感染和神经元死亡。
单细胞RNA测序揭示了与单核吞噬细胞亚群的保护性，与有害性贡献相关的转录特征。在人类脑类器官中，小胶质细胞也促进了神经保护性的转录变化和感染清除。因此，小胶质细胞在出生前具有保护作用，与原始巨噬细胞和单核细胞的促进疾病作用形成对比。基因分歧的ZIKV对髓系细胞表型的差异性调节，凸显了免疫细胞在胎儿感染过程中调节不同结果的潜力。
据悉，胎儿免疫细胞在先天性感染中的功能尚不完全明了。ZIKV可以通过母婴垂直传播，导致神经系统感染和先天性寨卡病毒综合症（CZS）。
附：英文原文
Title: Differential contributions of fetal mononuclear phagocytes to Zika virus neuroinvasion versus neuroprotection during congenital infection
Author: Muhammad Abdelbasset, Wilfried A.A. Saron, Dongliang Ma, Abhay P.S. Rathore, Tatsuya Kozaki, Chengwei Zhong, Chinmay Kumar Mantri, Yingrou Tan, Chi-Ching Tung, Hong Liang Tey, Justin Jang Hann Chu, Jinmiao Chen, Lai Guan Ng, Hongyan Wang, Florent Ginhoux, Ashley L. St. John
Issue&Volume: 2024-11-11
Abstract: Fetal immune cell functions during congenital infections are poorly understood. Zika virus (ZIKV) can vertically transmit from mother to fetus, causing nervous system infection and congenital ZIKV syndrome (CZS). We identified differential functional roles for fetal monocyte/macrophage cell types and microglia in ZIKV dissemination versus clearance using mouse models. Trafficking of ZIKV-infected primitive macrophages from the yolk sac allowed initial fetal virus inoculation, while recruited monocytes promoted non-productive neuroinflammation. Conversely, brain-resident differentiated microglia were protective, limiting infection and neuronal death. Single-cell RNA sequencing identified transcriptional profiles linked to the protective versus detrimental contributions of mononuclear phagocyte subsets. In human brain organoids, microglia also promoted neuroprotective transcriptional changes and infection clearance. Thus, microglia are protective before birth, contrasting with the disease-enhancing roles of primitive macrophages and monocytes. Differential modulation of myeloid cell phenotypes by genetically divergent ZIKVs underscores the potential of immune cells to regulate diverse outcomes during fetal infections.
DOI: 10.1016/j.cell.2024.10.028
Source: https://www.cell.com/cell/abstract/S0092-8674(24)01210-8