Spatial mapping reveals granuloma diversity and histopathological superstructure in human tuberculosis

Area of Science:

• Immunology
• Pathology
• Cellular Biology

Background:

• Tuberculosis (TB) is characterized by granulomas, but their tissue-wide heterogeneity at the single-cell level in human lungs remains unclear.
• Understanding the spatial organization of immune cells within TB lesions is crucial for deciphering disease progression and immune responses.

Purpose of the Study:

• To spatially resolve the heterogeneity of immune cell aggregates in human TB lung tissue at the single-cell level.
• To characterize the diversity and organization of non-necrotizing cellular lesions in relation to necrotizing granulomas.

Main Methods:

• Spatially mapping individual immune cells across entire human TB lung tissue sections.
• Analyzing cellular composition and spatial distribution of B cells and macrophages within lesions.

Main Results:

• Human TB lungs exhibit abundant non-necrotizing leukocyte aggregates alongside necrotizing granulomas.
• Non-necrotizing lesions display greater diversity and can be stratified into four classes based on immune cell composition and spatial arrangement.
• The composition of non-necrotizing structures correlates with proximity to necrotizing lesions, suggesting distinct, adjacent immune reactions.

Conclusions:

• Human TB lung pathology involves a complex histopathological superstructure of at least four types of non-necrotizing cellular aggregates.
• These non-necrotizing aggregates are organized as satellites surrounding necrotizing granulomas, indicating intricate spatial immune organization in TB.
• This spatial resolution provides a deeper understanding of the multifaceted immune landscape within TB-affected lung tissue.