The immunoregulatory landscape of human tuberculosis granulomas.

Erin F McCaffrey; Michele Donato; Leeat KerenZhenghao ChenAlea DelmastroMegan B FitzpatrickSanjana GuptaNoah F GreenwaldAlex BaranskiWilliam GrafRashmi KumarMarc BosseChristine Camacho FullawayPratista K RamdialErna ForgóVladimir JojicDavid Van ValenSmriti MehraShabaana A KhaderSean C BendallMatt van de RijnDaniel KalmanDeepak KaushalRobert L HunterNiaz BanaeiAdrie J C SteynPurvesh KhatriMichael Angelo

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The immunoregulatory landscape of human tuberculosis granulomas.

机译：The immunoregulatory landscape of human tuberculosis granulomas.

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Tuberculosis (TB) in humans is characterized by formation of immune-rich granulomas in infected tissues, the architecture and composition of which are thought to affect disease outcome. However, our understanding of the spatial relationships that control human granulomas is limited. Here, we used multiplexed ion beam imaging by time of flight (MIBI-TOF) to image 37 proteins in tissues from patients with active TB. We constructed a comprehensive atlas that maps 19 cell subsets across 8 spatial microenvironments. This atlas shows an IFN-γ-depleted microenvironment enriched for TGF-β, regulatory T cells and IDO1~(+)PD-L1~(+)myeloid cells. In a further transcriptomic meta-analysis of peripheral blood from patients with TB, immunoregulatory trends mirror those identified by granuloma imaging. Notably, PD-L1 expression is associated with progression to active TB and treatment response. These data indicate that in TB granulomas, there are local spatially coordinated immunoregulatory programs with systemic manifestations that define active TB.

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《Nature immunology》 |2022年第2期|318-329|共12页
作者
Erin F McCaffrey; Michele Donato; Leeat KerenZhenghao ChenAlea DelmastroMegan B FitzpatrickSanjana GuptaNoah F GreenwaldAlex BaranskiWilliam GrafRashmi KumarMarc BosseChristine Camacho FullawayPratista K RamdialErna ForgóVladimir JojicDavid Van ValenSmriti MehraShabaana A KhaderSean C BendallMatt van de RijnDaniel KalmanDeepak KaushalRobert L HunterNiaz BanaeiAdrie J C SteynPurvesh KhatriMichael Angelo;
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Calico Life Sciences LLC;

Division of Biology and Bioengineering, California Institute of Technology;

Texas Biomedical Research InstituteDepartment of Molecular Microbiology, Washington University School of MedicineDepartment of Pathology, Stanford University School of MedicineDepartment of Pathology and Laboratory Medicine, Emory University School of MedicineSouthwest National Primate Research Center, Texas Biomedical Research InstituteDepartment of Pathology and Laboratory Medicine, University of Texas Health Sciences Center atAfrica Health Research Institute, University of KwaZulu-NatalDepartment of Medicine, Division of Biomedical Informatics Research, Stanford University School ofDepartment of Molecular Cell Biology, Weizmann Institute of ScienceDepartment of Pathology, University of Wisconsin;

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中图分类医学免疫学;
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The immunoregulatory landscape of human tuberculosis granulomas.

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