Academic Journal
The immunoregulatory landscape of human tuberculosis granulomas
| العنوان: | The immunoregulatory landscape of human tuberculosis granulomas |
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| المؤلفون: | McCaffrey, Erin F., Donato, Michele, Keren, Leeat, Chen, Zhenghao, Delmastro, Alea, Fitzpatrick, Megan B., Gupta, Sanjana, Greenwald, Noah F., Baranski, Alex, Graf, William, Kumar, Rashmi, Bosse, Marc, Fullaway, Christine Camacho, Ramdial, Pratista K., Forgó, Erna, Jojic, Vladimir, Van Valen, David, Mehra, Smriti, Khader, Shabaana A., Bendall, Sean C., van de Rijn, Matt, Kalman, Daniel, Kaushal, Deepak, Hunter, Robert L., Banaei, Niaz, Steyn, Adrie J. C., Khatri, Purvesh, Angelo, Michael |
| المساهمون: | U.S. Department of Defense, Wellcome Trust, Bill and Melinda Gates Foundation, U.S. Department of Health & Human Services | National Institutes of Health, Cancer Research Institute, Parker Center for Cancer Immunotherapy, Breast Cancer Research Foundation, National Science Foundation, Damon Runyon Cancer Research Foundation, European Molecular Biology Organization, U.S. Department of Health & Human Services | NIH | National Cancer Institute, CRDF Global, South African Medical Research Council, U.S. Department of Health & Human Services | NIH | National Institute of Allergy and Infectious Diseases, Dr. Ralph and Marian Falk Medical Research Trust |
| المصدر: | Nature Immunology ; volume 23, issue 2, page 318-329 ; ISSN 1529-2908 1529-2916 |
| بيانات النشر: | Springer Science and Business Media LLC |
| سنة النشر: | 2022 |
| الوصف: | 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. |
| نوع الوثيقة: | article in journal/newspaper |
| اللغة: | English |
| DOI: | 10.1038/s41590-021-01121-x |
| الاتاحة: | http://dx.doi.org/10.1038/s41590-021-01121-x https://www.nature.com/articles/s41590-021-01121-x.pdf https://www.nature.com/articles/s41590-021-01121-x |
| Rights: | https://creativecommons.org/licenses/by/4.0 ; https://creativecommons.org/licenses/by/4.0 |
| رقم الانضمام: | edsbas.1796B21A |
| قاعدة البيانات: | BASE |
| DOI: | 10.1038/s41590-021-01121-x |
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