A protective role for eosinophils in host resistance to Mycobacterium tuberculosis. A protective role for eosinophils in host resistance to Mycobacterium tuberculosis

Host resistance to Mycobacterium tuberculosis (Mtb) infection requires the activities of multiple leukocyte subsets, yet the roles of the different innate effector cells during tuberculosis (TB) are incompletely understood. Here we show a role for eosinophils in host resistance to Mtb infection. In humans, eosinophils are found in resected human TB lung lesions and autopsy granulomas. Eosinophils are also found in granulomas in zebrafish, mice, and non-human primates, where they are functionally activated and degranulate. Transcriptional profiling of lung tissue after Mtb infection of mice, that selectively lack eosinophils, revealed changes in neuronal associated pathways. Importantly, employing several independent models of eosinophil deficiency in mice, we demonstrate that eosinophils are required for optimal pulmonary bacterial control and host survival after Mtb infection. Collectively, our findings establish an unexpected role for eosinophils, granulocytes typically associated with type II inflammation, in host resistance against Mtb, a major human bacterial pathogen. Overall design: 18 C57BL/6 mouses with and without eosinophils were infected with TB

宿主抗结核分枝杆菌（Mycobacterium tuberculosis, Mtb）感染依赖于多种白细胞亚群的功能活性，但目前对于不同固有免疫效应细胞在结核病（tuberculosis, TB）病程中的作用仍未完全阐明。本研究揭示了嗜酸性粒细胞（eosinophils）在宿主抗Mtb感染中的关键作用。在人体样本中，嗜酸性粒细胞可在切除的结核肺病灶以及尸检肉芽肿中被检出。在斑马鱼、小鼠以及非人灵长类动物的肉芽肿中同样存在嗜酸性粒细胞，且这些细胞处于功能活化状态并发生脱颗粒。对选择性缺失嗜酸性粒细胞的小鼠进行Mtb感染后，对其肺组织进行转录组谱分析，结果显示神经元相关通路发生显著改变。值得注意的是，本研究通过多种独立的小鼠嗜酸性粒细胞缺失模型证实，嗜酸性粒细胞是Mtb感染后实现最优肺部细菌清除以及宿主存活所必需的。综上，本研究结果证实了嗜酸性粒细胞——一类通常与II型炎症相关的粒细胞——在宿主抗主要人类细菌性病原体Mtb感染中的意外功能。实验设计概述：对18只C57BL/6小鼠（分别带有或缺失嗜酸性粒细胞）进行结核分枝杆菌感染。