Spatial mapping reveals granuloma diversity and histopathological superstructure in human tuberculosis

Author:

Sawyer Andrew J.123ORCID,Patrick Ellis456ORCID,Edwards Jarem17ORCID,Wilmott James S.137ORCID,Fielder Timothy8ORCID,Yang Qianting9ORCID,Barber Daniel L.1011ORCID,Ernst Joel D.12ORCID,Britton Warwick J.213ORCID,Palendira Umaimainthan123ORCID,Chen Xinchun1415ORCID,Feng Carl G.12316ORCID

Affiliation:

1. School of Medical Sciences, Faculty of Medicine and Health, The University of Sydney 1 , Sydney, Australia

2. Centenary Institute, The University of Sydney 2 , Sydney, Australia

3. Charles Perkins Centre, The University of Sydney 3 , Sydney, Australia

4. School of Mathematics and Statistics, Faculty of Science, The University of Sydney 4 , Sydney, Australia

5. Centre for Cancer Research, Westmead Institute for Medical Research, The University of Sydney 5 , Westmead, Australia

6. Sydney Precision Data Science Centre, The University of Sydney 6 , Sydney, Australia

7. Melanoma Institute Australia, The University of Sydney 7 , Sydney, Australia

8. Department of Tissue Pathology and Diagnostic Oncology, Royal Prince Alfred Hospital 8 , Camperdown, Australia

9. Guangdong Key Lab for Diagnosis and Treatment of Emerging Infectious Diseases, Shenzhen, Third People’s Hospital, Shenzhen 9 , Shenzhen, China

10. Laboratory of Parasitic Diseases, National Institute of Allergy and Infectious Diseases 10 , , Bethesda, MD, USA

11. National Institutes of Health 10 , , Bethesda, MD, USA

12. Division of Experimental Medicine, Department of Medicine, University of California San Francisco 11 , San Francisco, CA, USA

13. Department of Clinical Immunology, Royal Prince Alfred Hospital 12 , Camperdown, Australia

14. Guangdong Key Laboratory of Regional Immunity and Diseases, Department of Pathogen Biology, Shenzhen University 13 , Shenzhen, China

15. School of Medicine 13 , Shenzhen, China

16. Institute for Infectious Diseases, The University of Sydney 14 , Sydney, Australia

Abstract

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.

Funder

National Institutes of Health

Natural Science Foundation of China

Australian Postgraduate Awards

Publisher

Rockefeller University Press

Subject

Immunology,Immunology and Allergy

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