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Immune mapping of human tuberculosis and sarcoidosis lung granulomas
Stockholm University, Faculty of Science, Department of Biochemistry and Biophysics. Stockholm University, Science for Life Laboratory (SciLifeLab).
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Number of Authors: 172024 (English)In: Frontiers in Immunology, E-ISSN 1664-3224, Vol. 14, article id 1332733Article in journal (Refereed) Published
Abstract [en]

Tuberculosis (TB) and sarcoidosis are both granulomatous diseases. Here, we compared the immunological microenvironments of granulomas from TB and sarcoidosis patients using in situ sequencing (ISS) transcriptomic analysis and multiplexed immunolabeling of tissue sections. TB lesions consisted of large necrotic and cellular granulomas, whereas “multifocal” granulomas with macrophages or epitheloid cell core and a T-cell rim were observed in sarcoidosis samples. The necrotic core in TB lesions was surrounded by macrophages and encircled by a dense T-cell layer. Within the T-cell layer, compact B-cell aggregates were observed in most TB samples. These B-cell clusters were vascularized and could contain defined B-/T-cell and macrophage-rich areas. The ISS of 40–60 immune transcripts revealed the enriched expression of transcripts involved in homing or migration to lymph nodes, which formed networks at single-cell distances in lymphoid areas of the TB lesions. Instead, myeloid-annotated regions were enriched in CD68CD14ITGAMITGAX, and CD4 mRNA. CXCL8 and IL1B mRNA were observed in granulocytic areas in which M. tuberculosis was also detected. In line with ISS data indicating tertiary lymphoid structures, immune labeling of TB sections expressed markers of high endothelial venules, follicular dendritic cells, follicular helper T cells, and lymph-node homing receptors on T cells. Neither ISS nor immunolabeling showed evidence of tertiary lymphoid aggregates in sarcoidosis samples. Together, our finding suggests that despite their heterogeneity, the formation of tertiary immune structures is a common feature in granulomas from TB patients.

Place, publisher, year, edition, pages
2024. Vol. 14, article id 1332733
Keywords [en]
tuberculosis, sarcoidosis, granuloma, spatial transcriptomics, inducible bronchus associated lymphoid tissue, lung
National Category
Immunology in the medical area Cancer and Oncology
Identifiers
URN: urn:nbn:se:su:diva-227427DOI: 10.3389/fimmu.2023.1332733ISI: 001169030000001PubMedID: 38385142Scopus ID: 2-s2.0-85185475342OAI: oai:DiVA.org:su-227427DiVA, id: diva2:1844275
Available from: 2024-03-13 Created: 2024-03-13 Last updated: 2024-03-13Bibliographically approved

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Yokota, Chika

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