Organ-Specific Fate, Recruitment, and Refilling Dynamics of Tissue-Resident Macrophages during Blood-Stage Malaria
Organ-Specific Fate, Recruitment, and Refilling Dynamics of Tissue-Resident Macrophages during Blood-Stage Malaria
复制标题
DOI：
10.1016/j.celrep.2018.11.059
复制
发表时间：
2018-12-11
期刊：
影响因子：
8.8
通讯作者：
Ruedl, Christiane
中科院分区：
文献类型：
--
作者：
Lai, Si Min;Sheng, Jianpeng;Ruedl, Christiane
炎症诱导的组织驻留巨噬细胞的消失代表了关键的病原体防御机制。使用系统性血液阶段疟疾的模型，我们研究了多个器官中组织驻留巨噬细胞的动态，以确定它们在疾病过程中如何耗尽和重新填充。我们表明，疟原虫感染的结果在一个短暂的损失胚胎建立常驻巨噬细胞之前的寄生虫血症高峰。命运映射分析表明，炎症单核细胞有助于脾红髓巨噬细胞和肝枯否细胞的空龛的再增殖，而肺泡巨噬细胞主要通过自我更新重新填充其龛。有趣的是，脾脏和肝脏的局部微环境可以将胎儿来源的巨噬细胞的分子特征“印记”在新分化的骨髓来源的移民上，具有非常相似的基因表达谱和转换动力学。因此，单核吞噬细胞系统已经开发出独特但有效的组织特异性策略来补充空的壁龛，以保证系统的功能完整性。
Inflammation-induced disappearance of tissue-resident macrophages represents a key pathogen defense mechanism. Using a model of systemic blood-stage malaria, we studied the dynamics of tissue-resident macrophages in multiple organs to determine how they are depleted and refilled during the course of disease. We show that Plasmodium infection results in a transient loss of embryonically established resident macrophages prior to the parasitemia peak. Fate-mapping analysis reveals that inflammatory monocytes contribute to the repopulation of the emptied niches of splenic red pulp macrophages and hepatic Kupffer cells, while lung alveolar macrophages refill their niche predominantly through self-renewal. Interestingly, the local microenvironment of the spleen and liver can "imprint'' the molecular characteristics of fetal-derived macrophages on newly differentiated bone marrow-derived immigrants with remarkably similar gene expression profiles and turnover kinetics. Thus, the mononuclear phagocytic system has developed distinct but effective tissue-specific strategies to replenish emptied niches to guarantee the functional integrity of the system.