Spatial mapping reveals granuloma diversity and histopathological superstructure in human tuberculosis

作者：Andrew J. Sawyer, Ellis Patrick, Jarem J. Edwards, James S. Wilmott, Timothy Fielder, Qianting Yang, Daniel L. Barber, J. Ernst, Warwick J. Britton, Umaimainthan Palendira, Xinchun Chen, Carl G. Feng · 发表于：The Journal of Experimental Medicine · 年份：2023 · DOI：10.1084/jem.20221392 · 被引用次数：79 · 研究领域：Tuberculosis Research and Epidemiology、Mycobacterium research and diagnosis、Infectious Diseases and Tuberculosis

The hallmark of tuberculosis (TB) is the formation of immune cell-enriched aggregates called granulomas. While granulomas are pathologically diverse, their tissue-wide heterogeneity has not been spatially resolved at the single-cell level in human tissues. By spatially mapping individual immune cells in every lesion across entire tissue sections, we report that in addition to necrotizing granulomas, the human TB lung contains abundant non-necrotizing leukocyte aggregates surrounding areas of necrotizing tissue. These cellular lesions were more diverse in composition than necrotizing lesions and could be stratified into four general classes based on cellular composition and spatial distribution of B cells and macrophages. The cellular composition of non-necrotizing structures also correlates with their proximity to necrotizing lesions, indicating these are foci of distinct immune reactions adjacent to necrotizing granulomas. Together, we show that during TB, diseased lung tissue develops a histopathological superstructure comprising at least four different types of non-necrotizing cellular aggregates organized as satellites of necrotizing granulomas.