دورية أكاديمية
The cellular architecture of the antimicrobial response network in human leprosy granulomas.
| العنوان: | The cellular architecture of the antimicrobial response network in human leprosy granulomas. |
|---|---|
| المؤلفون: | Ma F; Division of Dermatology, Department of Medicine, University of California Los Angeles, Los Angeles, CA, USA.; Department of Microbiology, Immunology and Molecular Genetics, University of California Los Angeles, Los Angeles, CA, USA.; Department of Molecular, Cell and Developmental Biology, University of California Los Angeles, Los Angeles, CA, USA., Hughes TK; Institute for Medical Engineering & Science and Department of Chemistry, MIT, Cambridge, MA, USA.; Department of Immunology, Harvard Medical School, Boston, MA, USA.; Broad Institute of MIT and Harvard, Cambridge, MA, USA.; Ragon Institute of Massachusetts General Hospital MIT and Harvard, Cambridge, MA, USA., Teles RMB; Division of Dermatology, Department of Medicine, University of California Los Angeles, Los Angeles, CA, USA., Andrade PR; Division of Dermatology, Department of Medicine, University of California Los Angeles, Los Angeles, CA, USA., de Andrade Silva BJ; Division of Dermatology, Department of Medicine, University of California Los Angeles, Los Angeles, CA, USA., Plazyo O; Department of Dermatology, University of Michigan, Ann Arbor, MI, USA., Tsoi LC; Department of Dermatology, University of Michigan, Ann Arbor, MI, USA., Do T; Division of Dermatology, Department of Medicine, University of California Los Angeles, Los Angeles, CA, USA., Wadsworth MH 2nd; Institute for Medical Engineering & Science and Department of Chemistry, MIT, Cambridge, MA, USA.; Broad Institute of MIT and Harvard, Cambridge, MA, USA.; Ragon Institute of Massachusetts General Hospital MIT and Harvard, Cambridge, MA, USA., Oulee A; Division of Dermatology, Department of Medicine, University of California Los Angeles, Los Angeles, CA, USA., Ochoa MT; Department of Dermatology, University of Southern California, Los Angeles, CA, USA., Sarno EN; Leprosy Laboratory, Oswaldo Cruz Foundation, Rio de Janeiro, Brazil., Iruela-Arispe ML; Department of Cell and Developmental Biology, Northwestern University, Feinberg School of Medicine, Chicago, IL, USA., Klechevsky E; Department of Pathology and Immunology, Washington University School of Medicine, St. Louis, MO, USA., Bryson B; Ragon Institute of Massachusetts General Hospital MIT and Harvard, Cambridge, MA, USA.; Department of Biological Engineering, MIT, Cambridge, MA, USA., Shalek AK; Institute for Medical Engineering & Science and Department of Chemistry, MIT, Cambridge, MA, USA.; Department of Immunology, Harvard Medical School, Boston, MA, USA.; Broad Institute of MIT and Harvard, Cambridge, MA, USA.; Ragon Institute of Massachusetts General Hospital MIT and Harvard, Cambridge, MA, USA., Bloom BR; Department of Immunology and Infectious Diseases, Harvard T.H. Chan School of Public Health, Boston, MA, USA., Gudjonsson JE; Department of Dermatology, University of Michigan, Ann Arbor, MI, USA., Pellegrini M; Department of Molecular, Cell and Developmental Biology, University of California Los Angeles, Los Angeles, CA, USA., Modlin RL; Division of Dermatology, Department of Medicine, University of California Los Angeles, Los Angeles, CA, USA. rmodlin@mednet.ucla.edu.; Department of Microbiology, Immunology and Molecular Genetics, University of California Los Angeles, Los Angeles, CA, USA. rmodlin@mednet.ucla.edu. |
| المصدر: | Nature immunology [Nat Immunol] 2021 Jul; Vol. 22 (7), pp. 839-850. Date of Electronic Publication: 2021 Jun 24. |
| نوع المنشور: | Journal Article; Research Support, N.I.H., Extramural; Research Support, Non-U.S. Gov't |
| اللغة: | English |
| بيانات الدورية: | Publisher: Nature America Inc Country of Publication: United States NLM ID: 100941354 Publication Model: Print-Electronic Cited Medium: Internet ISSN: 1529-2916 (Electronic) Linking ISSN: 15292908 NLM ISO Abbreviation: Nat Immunol Subsets: MEDLINE |
| أسماء مطبوعة: | Original Publication: New York, NY : Nature America Inc. c2000- |
| مواضيع طبية MeSH: | Leprosy, Lepromatous/*immunology , Leprosy, Tuberculoid/*immunology , Mycobacterium leprae/*immunology , Skin/*immunology, Adolescent ; Adult ; Aged ; Female ; Fibroblasts/immunology ; Fibroblasts/microbiology ; Fibroblasts/pathology ; Gene Expression Profiling ; Host-Pathogen Interactions ; Humans ; Keratinocytes/immunology ; Keratinocytes/microbiology ; Keratinocytes/pathology ; Leprosy, Lepromatous/genetics ; Leprosy, Lepromatous/microbiology ; Leprosy, Lepromatous/pathology ; Leprosy, Tuberculoid/genetics ; Leprosy, Tuberculoid/microbiology ; Leprosy, Tuberculoid/pathology ; Macrophages/immunology ; Macrophages/microbiology ; Macrophages/pathology ; Male ; Middle Aged ; Mycobacterium leprae/pathogenicity ; RNA-Seq ; Single-Cell Analysis ; Skin/microbiology ; Skin/pathology ; T-Lymphocytes/immunology ; T-Lymphocytes/microbiology ; T-Lymphocytes/pathology ; Transcriptome |
| مستخلص: | Granulomas are complex cellular structures composed predominantly of macrophages and lymphocytes that function to contain and kill invading pathogens. Here, we investigated the single-cell phenotypes associated with antimicrobial responses in human leprosy granulomas by applying single-cell and spatial sequencing to leprosy biopsy specimens. We focused on reversal reactions (RRs), a dynamic process whereby some patients with disseminated lepromatous leprosy (L-lep) transition toward self-limiting tuberculoid leprosy (T-lep), mounting effective antimicrobial responses. We identified a set of genes encoding proteins involved in antimicrobial responses that are differentially expressed in RR versus L-lep lesions and regulated by interferon-γ and interleukin-1β. By integrating the spatial coordinates of the key cell types and antimicrobial gene expression in RR and T-lep lesions, we constructed a map revealing the organized architecture of granulomas depicting compositional and functional layers by which macrophages, T cells, keratinocytes and fibroblasts can each contribute to the antimicrobial response. |
| التعليقات: | Comment in: Cell Mol Immunol. 2022 May;19(5):558-560. (PMID: 34992283) |
| References: | Gordon, S. Alternative activation of macrophages. Nat. Rev. Immunol. 3, 23–35 (2003). (PMID: 1251187310.1038/nri978) Ridley, D. S. & Jopling, W. H. Classification of leprosy according to immunity. A five-group system. Int. J. Lepr. Other Mycobact. Dis. 34, 255–273 (1966). (PMID: 5950347) Modlin, R. L., Hofman, F. M., Taylor, C. R. & Rea, T. H. T lymphocyte subsets in the skin lesions of patients with leprosy. J. Am. Acad. Dermatol. 8, 182–189 (1983). (PMID: 621913610.1016/S0190-9622(83)70021-6) Stenger, S. et al. Differential effects of cytolytic T cell subsets on intracellular infection. Science 276, 1684–1687 (1997). (PMID: 918007510.1126/science.276.5319.1684) Stenger, S. et al. An antimicrobial activity of cytolytic T cells mediated by granulysin. Science 282, 121–125 (1998). (PMID: 975647610.1126/science.282.5386.121) Ochoa, M. T. et al. T-cell release of granulysin contributes to host defense in leprosy. Nat. Med. 7, 174–179 (2001). (PMID: 1117584710.1038/84620) Montoya, D. et al. Divergence of macrophage phagocytic and antimicrobial programs in leprosy. Cell Host Microbe 6, 343–353 (2009). (PMID: 19837374276455810.1016/j.chom.2009.09.002) Cooper, C. L. et al. Analysis of naturally occurring delayed-type hypersensitivity reactions in leprosy by in situ hybridization. J. Exp. Med. 169, 1565–1581 (1989). (PMID: 252395210.1084/jem.169.5.1565) Yamamura, M. et al. Defining protective responses to pathogens: cytokine profiles in leprosy lesions. Science 254, 277–279 (1991). (PMID: 192558210.1126/science.254.5029.277) Yamamura, M. et al. Cytokine patterns of immunologically mediated tissue damage. J. Immunol. 149, 1470–1475 (1992). (PMID: 1500726) Teles, R. M. B. et al. Type I interferon suppresses type II interferon-triggered human anti-mycobacterial responses. Science 339, 1448–1453 (2013). (PMID: 23449998365358710.1126/science.1233665) Liu, P. T. et al. Toll-like receptor triggering of a vitamin D-mediated human antimicrobial response. Science 311, 1770–1773 (2006). (PMID: 1649788710.1126/science.1123933) Fabri, M. et al. Vitamin D is required for IFN-γ-mediated antimicrobial activity of human macrophages. Sci. Transl. Med. 3, 104ra102 (2011). (PMID: 21998409326921010.1126/scitranslmed.3003045) Ochoa, M. T. et al. Role of granulysin in immunity to leprosy. Lepr. Rev. 71, S115 (2000). (PMID: 11201866) Dang, A. T. et al. IL-26 contributes to host defense against intracellular bacteria. J. Clin. Invest. 129, 1926–1939 (2019). (PMID: 30939123648635510.1172/JCI99550) Gierahn, T. M. et al. Seq-Well: portable, low-cost RNA sequencing of single cells at high throughput. Nat. Methods 14, 395–398 (2017). (PMID: 28192419537622710.1038/nmeth.4179) Butler, A., Hoffman, P., Smibert, P., Papalexi, E. & Satija, R. Integrating single-cell transcriptomic data across different conditions, technologies, and species. Nat. Biotechnol. 36, 411–420 (2018). (PMID: 29608179670074410.1038/nbt.4096) Tirosh, I. et al. Dissecting the multicellular ecosystem of metastatic melanoma by single-cell RNA-seq. Science 352, 189–196 (2016). (PMID: 27124452494452810.1126/science.aad0501) Balin, S. J. et al. Human antimicrobial cytotoxic T lymphocytes, defined by NK receptors and antimicrobial proteins, kill intracellular bacteria. Sci. Immunol. 3, eaat7668 (2018). (PMID: 30171080643123910.1126/sciimmunol.aat7668) Busch, M. et al. Lipoarabinomannan-responsive polycytotoxic T cells are associated with protection in human tuberculosis. Am. J. Respir. Crit. Care Med. 194, 345–355 (2016). (PMID: 26882070544110510.1164/rccm.201509-1746OC) Cochain, C. et al. Single-cell RNA-seq reveals the transcriptional landscape and heterogeneity of aortic macrophages in murine atherosclerosis. Circ. Res. 122, 1661–1674 (2018). (PMID: 2954536510.1161/CIRCRESAHA.117.312509) Jaitin, D. A. et al. Lipid-associated macrophages control metabolic homeostasis in a Trem2-dependent manner. Cell 178, 686–698.e14 (2019). (PMID: 31257031706868910.1016/j.cell.2019.05.054) Keren-Shaul, H. et al. A unique microglia type associated with restricting development of Alzheimer’s disease. Cell 169, 1276–1290.e17 (2017). (PMID: 2860235110.1016/j.cell.2017.05.018) Lavin, Y. et al. Innate immune landscape in early lung adenocarcinoma by paired single-cell analyses. Cell 169, 750–765.e17 (2017). (PMID: 28475900573793910.1016/j.cell.2017.04.014) Xue, D., Tabib, T., Morse, C. & Lafyatis, R. Transcriptome landscape of myeloid cells in human skin reveals diversity, rare populations and putative DC progenitors. J. Dermatol. Sci. 97, 41–49 (2020). (PMID: 3183627110.1016/j.jdermsci.2019.11.012) Wang, E. C. E., Dai, Z., Ferrante, A. W., Drake, C. G. & Christiano, A. M. A subset of TREM2 + dermal macrophages secretes oncostatin M to maintain hair follicle stem cell quiescence and inhibit hair growth. Cell Stem Cell 24, 654–669.e6 (2019). (PMID: 3093014610.1016/j.stem.2019.01.011) Xiong, X. et al. Landscape of intercellular crosstalk in healthy and NASH liver revealed by single-cell secretome gene analysis. Mol. Cell 75, 644–660.e5 (2019). (PMID: 31398325726268010.1016/j.molcel.2019.07.028) Esaulova, E. et al. The immune landscape in tuberculosis reveals populations linked to disease and latency. Cell Host Microbe 29, 165–178.e8 (2021). (PMID: 3334044910.1016/j.chom.2020.11.013) Tabib, T., Morse, C., Wang, T., Chen, W. & Lafyatis, R. SFRP2/DPP4 and FMO1/LSP1 define major fibroblast populations in human skin. J. Invest. Dermatol. 138, 802–810 (2018). (PMID: 2908067910.1016/j.jid.2017.09.045) He, H. et al. Single-cell transcriptome analysis of human skin identifies novel fibroblast subpopulation and enrichment of immune subsets in atopic dermatitis. J. Allergy Clin. Immunol. 145, 1615–1628 (2020). (PMID: 3203598410.1016/j.jaci.2020.01.042) Chen, Y., Rabson, A. B. & Gorski, D. H. MEOX2 regulates nuclear factor-κB activity in vascular endothelial cells through interactions with p65 and IκBβ. Cardiovasc. Res. 87, 723–731 (2010). (PMID: 20421348292080610.1093/cvr/cvq117) Trapnell, C. et al. The dynamics and regulators of cell fate decisions are revealed by pseudotemporal ordering of single cells. Nat. Biotechnol. 32, 381–386 (2014). (PMID: 24658644412233310.1038/nbt.2859) Wang, G., Li, X. & Wang, Z. APD3: the antimicrobial peptide database as a tool for research and education. Nucleic Acids Res. 44, D1087–D1093 (2016). (PMID: 2660269410.1093/nar/gkv1278) Solé-Boldo, L. et al. Single-cell transcriptomes of the human skin reveal age-related loss of fibroblast priming. Commun. Biol. 3, 188 (2020). (PMID: 32327715718175310.1038/s42003-020-0922-4) Meller, S. et al. T Iyer, A. M. et al. Leprosy-specific B-cells within cellular infiltrates in active leprosy lesions. Hum. Pathol. 38, 1065–1073 (2007). (PMID: 1744237810.1016/j.humpath.2006.12.017) Ochoa, M. T. et al. A role for interleukin-5 in promoting increased immunoglobulin M at the site of disease in leprosy. Immunology 131, 405–414 (2010). (PMID: 20561085299656110.1111/j.1365-2567.2010.03314.x) Montoya, D. J. et al. Dual RNA-seq of human leprosy lesions identifies bacterial determinants linked to host immune response. Cell Rep. 26, 3574–3585.e3 (2019). (PMID: 30917313650887110.1016/j.celrep.2019.02.109) Macosko, E. Z. et al. Highly parallel genome-wide expression profiling of individual cells using nanoliter droplets. Cell 161, 1202–1214 (2015). (PMID: 26000488448113910.1016/j.cell.2015.05.002) Dobin, A. et al. STAR: ultrafast universal RNA-seq aligner. Bioinformatics 29, 15–21 (2013). (PMID: 23104886) Young, M. D. & Behjati, S. SoupX removes ambient RNA contamination from droplet-based single-cell RNA sequencing data. Gigascience 9, giaa151 (2020). (PMID: 33367645776317710.1093/gigascience/giaa151) Teles, R. M. B. et al. Identification of a systemic interferon-γ inducible antimicrobial gene signature in leprosy patients undergoing reversal reaction. PLoS Negl. Trop. Dis. 13, e0007764 (2019). (PMID: 31600201680501410.1371/journal.pntd.0007764) Andrade, P. R. et al. The cell fate regulator NUPR1 is induced by Mycobacterium leprae via type I interferon in human leprosy. PLoS Negl. Trop. Dis. 13, e0007589 (2019). (PMID: 10.1371/journal.pntd.0007589) Wang, H. et al. Cellular, molecular, and immunological characteristics of Langhans multinucleated giant cells programmed by IL-15. J. Invest. Dermatol. 140, 1824–1836.e7 (2020). (PMID: 32092350822358610.1016/j.jid.2020.01.026) Waddell, S. J. et al. Dissecting interferon-induced transcriptional programs in human peripheral blood cells. PLoS ONE 5, e9753 (2010). (PMID: 20339534284229610.1371/journal.pone.0009753) Inkeles, M. S. et al. Cell-type deconvolution with immune pathways identifies gene networks of host defense and immunopathology in leprosy. JCI Insight 1, e88843 (2016). (PMID: 27699251503375710.1172/jci.insight.88843) Martinez, A. N. et al. Molecular determination of Mycobacterium leprae viability by use of real-time PCR. J. Clin. Microbiol. 47, 2124–2130 (2009). (PMID: 19439537270853210.1128/JCM.00512-09) |
| معلومات مُعتمدة: | R01 AR075959 United States AR NIAMS NIH HHS; P30 AR075043 United States AR NIAMS NIH HHS; R01 CA245277 United States CA NCI NIH HHS; R01 AR073252 United States AR NIAMS NIH HHS; R35 HL140014 United States HL NHLBI NIH HHS; U24 AI118672 United States AI NIAID NIH HHS; P50 AR080594 United States AR NIAMS NIH HHS; R01 AI022553 United States AI NIAID NIH HHS; R01 AR074302 United States AR NIAMS NIH HHS; R01 AR040312 United States AR NIAMS NIH HHS; T32 AR007197 United States AR NIAMS NIH HHS |
| تواريخ الأحداث: | Date Created: 20210625 Date Completed: 20210823 Latest Revision: 20230701 |
| رمز التحديث: | 20230701 |
| مُعرف محوري في PubMed: | PMC8579511 |
| DOI: | 10.1038/s41590-021-00956-8 |
| PMID: | 34168371 |
| قاعدة البيانات: | MEDLINE |
Find this article in full text from Springer Verlag. 
Full Text Finder | تدمد: | 1529-2916 |
|---|---|
| DOI: | 10.1038/s41590-021-00956-8 |