Department of Integrative Immunobiology, Duke University School of Medicine, Durham, United States.
Department of Ophthalmology, Duke University School of Medicine, Durham, United States.
Elife. 2024 Nov 14;13:RP96425. doi: 10.7554/eLife.96425.
Granulomas are defined by the presence of organized layers of immune cells that include macrophages. Granulomas are often characterized as a way for the immune system to contain an infection and prevent its dissemination. We recently established a mouse infection model where induces the innate immune system to form granulomas in the liver. This response successfully eradicates the bacteria and returns the liver to homeostasis. Here, we sought to characterize the chemokines involved in directing immune cells to form the distinct layers of a granuloma. We use spatial transcriptomics to investigate the spatial and temporal expression of all CC and CXC chemokines and their receptors within this granuloma response. The expression profiles change dynamically over space and time as the granuloma matures and then resolves. To investigate the importance of monocyte-derived macrophages in this immune response, we studied the role of CCR2 during infection. mice had negligible numbers of macrophages, but large numbers of neutrophils, in the -infected lesions. In addition, lesions had abnormal architecture resulting in loss of bacterial containment. Without CCR2, bacteria disseminated and the mice succumbed to the infection. This indicates that macrophages are critical to form a successful innate granuloma in response to .
肉芽肿是由包含巨噬细胞的有组织的免疫细胞层定义的。肉芽肿通常被认为是免疫系统控制感染并防止其传播的一种方式。我们最近建立了一种小鼠感染模型，其中 诱导先天免疫系统在肝脏中形成肉芽肿。这种反应成功地消灭了细菌并使肝脏恢复了稳态。在这里，我们试图描述指导免疫细胞形成肉芽肿不同层的趋化因子。我们使用空间转录组学来研究在这种肉芽肿反应中所有 CC 和 CXC 趋化因子及其受体的空间和时间表达。随着肉芽肿的成熟和消退，表达谱在空间和时间上动态变化。为了研究单核细胞衍生的巨噬细胞在这种免疫反应中的重要性，我们研究了 CCR2 在 感染中的作用。 在 感染的病变中，CCR2 缺失的小鼠巨噬细胞数量可忽略不计，但中性粒细胞数量却很多。此外，病变的结构异常导致细菌无法被控制。没有 CCR2，细菌就会扩散，小鼠就会死于感染。这表明巨噬细胞对于针对 的先天肉芽肿的形成至关重要。
