The immunoregulatory landscape of human tuberculosis granulomas.
Journal
Nature immunology
ISSN: 1529-2916
Titre abrégé: Nat Immunol
Pays: United States
ID NLM: 100941354
Informations de publication
Date de publication:
02 2022
02 2022
Historique:
received:
25
05
2021
accepted:
14
12
2021
pubmed:
22
1
2022
medline:
19
2
2022
entrez:
21
1
2022
Statut:
ppublish
Résumé
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
Identifiants
pubmed: 35058616
doi: 10.1038/s41590-021-01121-x
pii: 10.1038/s41590-021-01121-x
pmc: PMC8810384
doi:
Substances chimiques
B7-H1 Antigen
0
Cytokines
0
Indoleamine-Pyrrole 2,3,-Dioxygenase
0
Types de publication
Journal Article
Meta-Analysis
Research Support, N.I.H., Extramural
Research Support, Non-U.S. Gov't
Research Support, U.S. Gov't, Non-P.H.S.
Langues
eng
Sous-ensembles de citation
IM
Pagination
318-329Subventions
Organisme : NIAID NIH HHS
ID : R01 AI134810
Pays : United States
Organisme : NIAID NIH HHS
ID : U19 AI057229
Pays : United States
Organisme : NIAID NIH HHS
ID : U19 AI109662
Pays : United States
Organisme : NIAID NIH HHS
ID : R01 AI134245
Pays : United States
Organisme : NIAID NIH HHS
ID : R33 AI138280
Pays : United States
Organisme : NCI NIH HHS
ID : F31 CA246880
Pays : United States
Organisme : NIAID NIH HHS
ID : U19 AI167903
Pays : United States
Organisme : NIAID NIH HHS
ID : R01 AI125197
Pays : United States
Organisme : NIAID NIH HHS
ID : T32 AI007290
Pays : United States
Organisme : NIH HHS
ID : P51 OD011133
Pays : United States
Organisme : Wellcome Trust
Pays : United Kingdom
Commentaires et corrections
Type : ErratumIn
Informations de copyright
© 2022. The Author(s).
Références
World Health Organization. Global Tuberculosis Report 2020 https://www.who.int/publications/i/item/9789240013131 (WHO, 2020).
Cohen, S. B. et al. Alveolar macrophages provide an early Mycobacterium tuberculosis niche and initiate dissemination. Cell Host Microbe 24, 439–446 (2018).
pubmed: 30146391
pmcid: 6152889
doi: 10.1016/j.chom.2018.08.001
Wolf, A. J. et al. Mycobacterium tuberculosis infects dendritic cells with high frequency and impairs their function in vivo. J. Immunol. 179, 2509–2519 (2007).
doi: 10.4049/jimmunol.179.4.2509
pubmed: 17675513
Bold, T. D. & Ernst, J. D. Who benefits from granulomas, mycobacteria or host? Cell 136, 17–19 (2009).
pubmed: 19135882
pmcid: 4214211
doi: 10.1016/j.cell.2008.12.032
Davis, J. M. & Ramakrishnan, L. The role of the granuloma in expansion and dissemination of early tuberculous infectionspan. Cell 136, 37–49 (2009).
pubmed: 19135887
pmcid: 3134310
doi: 10.1016/j.cell.2008.11.014
Ramakrishnan, L. Revisiting the role of the granuloma in tuberculosis. Nat. Rev. Immunol. 12, 352–366 (2012).
doi: 10.1038/nri3211
pubmed: 22517424
Cadena, A. et al. Heterogeneity in tuberculosis.Nat. Rev. Immunol. 17, 691–702 (2017).
pubmed: 28736436
pmcid: 6247113
doi: 10.1038/nri.2017.69
Subbian, S. et al. Lesion-specific immune response in granulomas of patients with pulmonary tuberculosis: a pilot study. PLoS ONE 10, e0132249 (2015).
pubmed: 26133981
pmcid: 4489805
doi: 10.1371/journal.pone.0132249
Coleman, M. T. et al. Early changes by (18)fluorodeoxyglucose positron emission tomography coregistered with computed tomography predict outcome after Mycobacterium tuberculosis infection in cynomolgus macaques. Infect. Immun. 82, 2400–2404 (2014).
pubmed: 24664509
pmcid: 4019174
doi: 10.1128/IAI.01599-13
Lin, P. L. et al. Sterilization of granulomas is common in active and latent tuberculosis despite within-host variability in bacterial killing. Nat. Med. 20, 75–79 (2013).
pubmed: 24336248
pmcid: 3947310
doi: 10.1038/nm.3412
Martin, C. J. et al. Digitally Barcoding Mycobacterium tuberculosis reveals in vivo infection dynamics in the macaque model of tuberculosis. MBio 8, e00312–e00317 (2017).
pubmed: 28487426
pmcid: 5424202
doi: 10.1128/mBio.00312-17
Carow, B. et al. Spatial and temporal localization of immune transcripts defines hallmarks and diversity in the tuberculosis granuloma. Nat. Commun. 10, 1–15 (2019).
doi: 10.1038/s41467-019-09816-4
Marakalala, M. J. et al. Inflammatory signaling in human tuberculosis granulomas is spatially organized. Nat. Med. 22, 531–538 (2016).
pubmed: 27043495
pmcid: 4860068
doi: 10.1038/nm.4073
Kauffman, K. D. et al. Defective positioning in granulomas but not lung-homing limits CD4 T-cell interactions with Mycobacterium tuberculosis-infected macrophages in rhesus macaques. Mucosal Immunol. 11, 462–473 (2018).
doi: 10.1038/mi.2017.60
pubmed: 28745326
Ernst, J. D., Cornelius, A., Desvignes, L., Tavs, J. & Norris, B. A. Limited antimycobacterial efficacy of epitope peptide administration despite enhanced antigen-specific CD4 T-cell activation. J. Infect. Dis. 218, 1653–1662 (2018).
pubmed: 29548008
pmcid: 6173573
doi: 10.1093/infdis/jiy142
Keren, L. et al. MIBI-TOF: a multiplexed imaging platform relates cellular phenotypes and tissue structure. Sci. Adv. 5, eaax5851 (2019).
pubmed: 31633026
pmcid: 6785247
doi: 10.1126/sciadv.aax5851
Krishnan, N., Robertson, B. D. & Thwaites, G. The mechanisms and consequences of the extra-pulmonary dissemination of Mycobacterium tuberculosis. Tuberculosis 90, 361–366 (2010).
doi: 10.1016/j.tube.2010.08.005
pubmed: 20829117
Keren, L. et al. A structured tumor-immune microenvironment in triple negative breast cancer revealed by multiplexed ion beam imaging. Cell 174, 1373–1387 (2018).
pubmed: 30193111
pmcid: 6132072
doi: 10.1016/j.cell.2018.08.039
Van Valen, D. A. et al. Deep learning automates the quantitative analysis of individual cells in live-cell imaging experiments. PLoS Comput. Biol. 12, e1005177 (2016).
pubmed: 27814364
pmcid: 5096676
doi: 10.1371/journal.pcbi.1005177
Bannon, D. et al. DeepCell Kiosk: scaling deep learning–enabled cellular image analysis with Kubernetes. Nat. Methods 18, 43–45 (2021).
pubmed: 33398191
pmcid: 8759612
doi: 10.1038/s41592-020-01023-0
Van Gassen, S. et al. FlowSOM: using self-organizing maps for visualization and interpretation of cytometry data. Cytom. Part A 87, 636–645 (2015).
doi: 10.1002/cyto.a.22625
Polena, H. et al. Mycobacterium tuberculosis exploits the formation of new blood vessels for its dissemination. Sci. Rep. 6, 33162 (2016).
pubmed: 27616470
pmcid: 5018821
doi: 10.1038/srep33162
Oehlers, S. H. et al. Interception of host angiogenic signalling limits mycobacterial growth. Nature 517, 612–615 (2015).
doi: 10.1038/nature13967
pubmed: 25470057
Girvan, M. & Newman, M. E. J. Community structure in social and biological networks. Proc. Natl Acad. Sci. USA 99, 7821–7826 (2002).
pubmed: 12060727
pmcid: 122977
doi: 10.1073/pnas.122653799
Chen, Z., Soifer, I., Hilton, H., Keren, L. & Jojic, V. Modeling multiplexed images with spatial-LDA reveals novel tissue microenvironments. J. Comput. Biol. 27, 1204–1218 (2020).
pubmed: 32243203
pmcid: 7415889
doi: 10.1089/cmb.2019.0340
Shi, J. et al. PD-1 controls follicular T helper cell positioning and function. Immunity 49, 264–274 (2018).
pubmed: 30076099
pmcid: 6104813
doi: 10.1016/j.immuni.2018.06.012
Ulrichs, T. et al. Human tuberculous granulomas induce peripheral lymphoid follicle-like structures to orchestrate local host defence in the lung. J. Pathol. 204, 217–228 (2004).
doi: 10.1002/path.1628
pubmed: 15376257
Difazio, R. M. et al. Active transforming growth factor-β is associated with phenotypic changes in granulomas after drug treatment in pulmonary tuberculosis. DARU, J. Pharm. Sci. 24, 6 (2016).
Krystel-Whittemore, M. Mast cell: a multi-functional master cell. Front. Oncol. 6, 620 (2016).
Gideon, H. P. et al. Single-cell profiling of tuberculosis lung granulomas reveals functional lymphocyte. Preprint at bioRxiv https://doi.org/10.1101/2020.10.24.352492 (2020).
Shen, L. et al. PD-1/PD-L pathway inhibits M.tb-specific CD4+ T-cell functions and phagocytosis of macrophages in active tuberculosis. Sci. Rep. 6, 38362 (2016).
pubmed: 27924827
pmcid: 5141449
doi: 10.1038/srep38362
Mehra, S. et al. Granuloma correlates of protection against tuberculosis and mechanisms of immune modulation by Mycobacterium tuberculosis. J. Infect. Dis. 207, 1115–1127 (2013).
doi: 10.1093/infdis/jis778
pubmed: 23255564
Munn, D. H. & Mellor, A. L. IDO in the tumor microenvironment: inflammation, counter-regulation, and tolerance. Trends Immunol. 37, 193–207 (2016).
pubmed: 26839260
pmcid: 4916957
doi: 10.1016/j.it.2016.01.002
Gautam, U. S. et al. In vivo inhibition of tryptophan catabolism reorganizes the tuberculoma and augments immune-mediated control of Mycobacterium tuberculosis. Proc. Natl Acad. Sci. USA 115, E62–E71 (2018).
doi: 10.1073/pnas.1711373114
pubmed: 29255022
Jurado, J. O. et al. Programmed death (PD)-1:PD-ligand 1/PD-ligand 2 pathway inhibits T cell effector functions during human tuberculosis. J. Immunol. 181, 116–125 (2008).
doi: 10.4049/jimmunol.181.1.116
pubmed: 18566376
Mulder, K. Cross-tissue single-cell landscape of human monocytes and macrophages in health and disease. Immunity 54, 1883–1900 (2021).
doi: 10.1016/j.immuni.2021.07.007
pubmed: 34331874
Veglia, F., Perego, M. & Gabrilovich, D. Myeloid-derived suppressor cells coming of age review-article. Nat. Immunol. 19, 108–119 (2018).
pubmed: 29348500
pmcid: 5854158
doi: 10.1038/s41590-017-0022-x
Gideon, H. P., Phuah, J., Junecko, B. A. & Mattila, J. T. Neutrophils express pro- and anti-inflammatory cytokines in granulomas from Mycobacterium tuberculosis-infected cynomolgus macaques. Mucosal Immunol. 12, 1370–1381 (2019).
pubmed: 31434990
pmcid: 6824993
doi: 10.1038/s41385-019-0195-8
Kanamori, M., Nakatsukasa, H., Okada, M., Lu, Q. & Yoshimura, A. Induced regulatory T cells: their development, stability, and applications. Trends Immunol. 37, 803–811 (2016).
pubmed: 27623114
doi: 10.1016/j.it.2016.08.012
Scott-Browne, J. P. et al. Expansion and function of Foxp3-expressing T regulatory cells during tuberculosis. J. Exp. Med. 204, 2159–2169 (2007).
pubmed: 17709423
pmcid: 2118702
doi: 10.1084/jem.20062105
Guyot-Revol, V., Innes, J. A., Hackforth, S., Hinks, T. & Lalvani, A. Regulatory T cells are expanded in blood and disease sites in patients with tuberculosis. Am. J. Respir. Crit. Care Med. 173, 803–810 (2006).
doi: 10.1164/rccm.200508-1294OC
pubmed: 16339919
Green, A. M. et al. CD4 + regulatory T cells in a cynomolgus macaque model of Mycobacterium tuberculosis infection. J. Infect. Dis. 202, 533–541 (2010).
doi: 10.1086/654896
pubmed: 20617900
Bagaitkar, J. Cellular dynamics of resolving inflammation. Blood 124, 1701–1703 (2014).
pubmed: 25214196
pmcid: 4162102
doi: 10.1182/blood-2014-07-589341
Wherry, E. J. & Kurachi, M. Molecular and cellular insights into T cell exhaustion. Nat. Rev. Immunol. 15, 486–499 (2015).
pubmed: 26205583
pmcid: 4889009
doi: 10.1038/nri3862
Wong, E. A. Low levels of T cell exhaustion in tuberculous lung granulomas. Infect. Immun. 86, e00426-18 (2018).
pubmed: 29891540
pmcid: 6105875
doi: 10.1128/IAI.00426-18
Gern, B. H. et al. TGFβ restricts expansion, survival, and function of T cells within the tuberculous granuloma. Cell Host Microbe 29, 594–606 (2021).
doi: 10.1016/j.chom.2021.02.005
pubmed: 33711270
pmcid: 8624870
Baughman, R. P. Sarcoidosis.Lancet 361, 1111–1118 (2003).
doi: 10.1016/S0140-6736(03)12888-7
pubmed: 12672326
Koth, L. L. et al. Sarcoidosis blood transcriptome reflects lung inflammation and overlaps with tuberculosis. Am. J. Respir. Crit. Care Med. 184, 1153–1163 (2011).
pubmed: 21852540
pmcid: 3262024
doi: 10.1164/rccm.201106-1143OC
Maertzdorf, J. et al. Common patterns and disease-related signatures in tuberculosis and sarcoidosis. Proc. Natl Acad. Sci. USA 109, 7853–7858 (2012).
pubmed: 22547807
pmcid: 3356621
doi: 10.1073/pnas.1121072109
Rossi, G. A. et al. Helper T-lymphocytes in pulmonary sarcoidosis: functional analysis of a lung T-cell subpopulation in patients with active disease. Am. Rev. Respir. Dis. 133, 1086–1090 (1986).
Facco, M. et al. Sarcoidosis is a Th1/Th17 multisystem disorder. Thorax 66, 144–150 (2011).
doi: 10.1136/thx.2010.140319
pubmed: 21139119
Haynes, W. A. Empowering multi-cohort gene expression analysis to increase reproducibility. Pac. Symp. Biocomput. 22, 144–153 (2017).
pubmed: 27896970
Sweeney, T. E., Haynes, W. A., Vallania, F., Ioannidis, J. P. & Khatri, P. Methods to increase reproducibility in differential gene expression via meta-analysis. Nucleic Acids Res. (2017).
Scriba, T. J. et al. Sequential inflammatory processes define human progression from M. tuberculosis infection to tuberculosis disease. PLoS Pathog. 13, e1006687 (2017).
pubmed: 29145483
pmcid: 5689825
doi: 10.1371/journal.ppat.1006687
Zak, D. E. et al. A blood RNA signature for tuberculosis disease risk: a prospective cohort study. Lancet 387, 2312–2322 (2016).
pubmed: 27017310
pmcid: 5392204
doi: 10.1016/S0140-6736(15)01316-1
Warsinske, H., Vashisht, R. & Khatri, P. Host-response-based gene signatures for tuberculosis diagnosis: a systematic comparison of 16 signatures. PLoS Med. 16, e1002786 (2019).
pubmed: 31013272
pmcid: 6478271
doi: 10.1371/journal.pmed.1002786
Roy Chowdhury, R. et al. A multi-cohort study of the immune factors associated with M. tuberculosis infection outcomes. Nature 560, 644–648 (2018).
doi: 10.1038/s41586-018-0439-x
pubmed: 30135583
Malherbe, S. T. et al. Persisting positron emission tomography lesion activity and Mycobacterium tuberculosis mRNA after tuberculosis cure. Nat. Med. 22, 1094–1100 (2016).
pubmed: 27595324
pmcid: 5053881
doi: 10.1038/nm.4177
Collins, J. M. et al. Tryptophan catabolism reflects disease activity in human tuberculosis. JCI Insight 5, e137131 (2020).
pmcid: 7259525
doi: 10.1172/jci.insight.137131
Elkington, P. T., Bateman, A. C., Thomas, G. J. & Ottensmeier, C. H. Implications of tuberculosis reactivation after immune checkpoint inhibition. Am. J. Respiratory Crit. Care Med. 198, 1451–1453 (2018).
doi: 10.1164/rccm.201807-1250LE
Flynn, J. L., Goldstein, M. M., Triebold, K. J., Koller, B. & Bloom, B. R. Major histocompatibility complex class I-restricted T cells are required for resistance to Mycobacterium tuberculosis infection. Proc. Natl Acad. Sci. USA 89, 12013–12017 (1992).
pubmed: 1465432
pmcid: 50688
doi: 10.1073/pnas.89.24.12013
Lalvani, A. et al. Human cytolytic and interferon γ-secreting CD8
pubmed: 9419365
pmcid: 18198
doi: 10.1073/pnas.95.1.270
Li, M. O., Sanjabi, S. & Flavell, R. A. A. Transforming growth factor-β controls development, homeostasis, and tolerance of T cells by regulatory T cell-dependent and -independent mechanisms. Immunity 25, 455–471 (2006).
doi: 10.1016/j.immuni.2006.07.011
pubmed: 16973386
Jarnicki, A. G., Lysaght, J., Todryk, S. & Mills, K. H. G. Suppression of antitumor immunity by IL-10 and TGF-β-producing T cells infiltrating the growing tumor: influence of tumor environment on the induction of CD4 + and CD8 + regulatory T cells. J. Immunol. 177, 896–904 (2006).
doi: 10.4049/jimmunol.177.2.896
pubmed: 16818744
Wong, E. A. et al. IL-10 impairs local immune response in lung granulomas and lymph nodes during early Mycobacterium tuberculosis infection. J. Immunol. 204, 644–659 (2020).
doi: 10.4049/jimmunol.1901211
pubmed: 31862711
McNab, F. W. et al. Programmed death ligand 1 is over-expressed by neutrophils in the blood of patients with active tuberculosis. Eur. J. Immunol. 41, 1941–1947 (2011).
pubmed: 21509782
pmcid: 3179592
doi: 10.1002/eji.201141421
Matthew, P. R. Berry et al. An interferon-inducible neutrophil-driven blood transcriptional signature in human tuberculosis. Nature 466, 973–977 (2010).
doi: 10.1038/nature09247
Havel, J. J., Chowell, D. & Chan, T. A. The evolving landscape of biomarkers for checkpoint inhibitor immunotherapy. Nat. Rev. Cancer 19, 133–150 (2019).
pubmed: 30755690
pmcid: 6705396
doi: 10.1038/s41568-019-0116-x
Barber, D. L. et al. Tuberculosis following PD-1 blockade for cancer immunotherapy. Sci. Transl. Med. 11, eaat2702 (2019).
pubmed: 30651320
pmcid: 7372940
doi: 10.1126/scitranslmed.aat2702
Anastasopoulou, A., Ziogas, D. C., Samarkos, M., Kirkwood, J. M. & Gogas, H. Reactivation of tuberculosis in cancer patients following administration of immune checkpoint inhibitors: current evidence and clinical practice recommendations. J. Immunother. Cancer 7, 239 (2019).
pubmed: 31484550
pmcid: 6727332
doi: 10.1186/s40425-019-0717-7
Tezera, L. B. et al. Anti-PD-1 immunotherapy leads to tuberculosis reactivation via dysregulation of TNF-α. Elife 9, 52668 (2020).
doi: 10.7554/eLife.52668
Sharpe, A. H., Sher, A., Barber, D. L., Mayer-Barber, K. D. & Feng, C. G. CD4 T cells promote rather than control CD4 T cells promote rather than control tuberculosis in the absence of PD-1–mediated inhibition. J. Immunol. 6, 1598–1607 (2017).
Anand, K. et al. Mycobacterial infections due to PD-1 and PD-L1 checkpoint inhibitors. ESMO Open 5, e000866 (2020).
pubmed: 32817069
pmcid: 7437685
doi: 10.1136/esmoopen-2020-000866
Hartmann, F. J., et al. Multiplexed single-cell metabolic profiles organize the spectrum of cytotoxic human T cells. Preprint at bioRxiv https://doi.org/10.1101/2020.01.17.909796 (2020).
Hu, Z. et al. MetaCyto: a tool for automated meta-analysis of mass and flow cytometry data. Cell Rep. 24, 1377–1388 (2018).
pubmed: 30067990
pmcid: 6583920
doi: 10.1016/j.celrep.2018.07.003
Newman, M. E. J. Finding community structure in networks using the eigenvectors of matrices. Phys. Rev. E 74, 036104 (2006).
doi: 10.1103/PhysRevE.74.036104
McInnes, L., Healy, J. & Melville, J. UMAP: uniform manifold approximation and projection for dimension reduction. Preprint at https://arxiv.org/abs/1802.03426 (2018).
Bankhead, P. et al. QuPath: open source software for digital pathology image analysis. Sci. Rep. 2017, 16878 (2017).
doi: 10.1038/s41598-017-17204-5