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Spatial and temporal localization of immune transcripts defines hallmarks and diversity in the tuberculosis granuloma
Stockholm University, Faculty of Science, Department of Biochemistry and Biophysics. Stockholm University, Science for Life Laboratory (SciLifeLab).
Stockholm University, Faculty of Science, Department of Biochemistry and Biophysics. Stockholm University, Science for Life Laboratory (SciLifeLab).
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Number of Authors: 62019 (English)In: Nature Communications, ISSN 2041-1723, E-ISSN 2041-1723, Vol. 10, article id 1823Article in journal (Refereed) Published
Abstract [en]

Granulomas are the pathological hallmark of tuberculosis (TB) and the niche where bacilli can grow and disseminate or the immunological microenvironment in which host cells interact to prevent bacterial dissemination. Here we show 34 immune transcripts align to the morphology of lung sections from Mycobacterium tuberculosis-infected mice at cellular resolution. Colocalizing transcript networks at <10 mu m in C57BL/6 mouse granulomas increase complexity with time after infection. B-cell clusters develop late after infection. Transcripts from activated macrophages are enriched at subcellular distances from M. tuberculosis. Encapsulated C3HeB/FeJ granulomas show necrotic centers with transcripts associated with immunosuppression (Foxp3, Il10), whereas those in the granuloma rims associate with activated T cells and macrophages. We see highly diverse networks with common interactors in similar lesions. Different immune landscapes of M. tuberculosis granulomas depending on the time after infection, the histopathological features of the lesion, and the proximity to bacteria are here defined.

Place, publisher, year, edition, pages
2019. Vol. 10, article id 1823
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Biological Sciences
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URN: urn:nbn:se:su:diva-169112DOI: 10.1038/s41467-019-09816-4ISI: 000465200000004PubMedID: 31015452OAI: oai:DiVA.org:su-169112DiVA, id: diva2:1321265
Available from: 2019-06-07 Created: 2019-06-07 Last updated: 2019-06-07Bibliographically approved

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