Spatial mapping reveals granuloma diversity and histopathological superstructure in human tuberculosis

Autor: Andrew J. Sawyer, Ellis Patrick, Jarem Edwards, James S. Wilmott, Timothy Fielder, Qianting Yang, Daniel L. Barber, Joel D. Ernst, Warwick J. Britton, Umaimainthan Palendira, Xinchun Chen, Carl G. Feng
Rok vydání: 2023
Předmět:
Zdroj: Journal of Experimental Medicine. 220
ISSN: 1540-9538
0022-1007
DOI: 10.1084/jem.20221392
Popis: 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.
Databáze: OpenAIRE