دورية أكاديمية
أعرض في EDS

A Macrophage Response to Mycobacterium leprae Phenolic Glycolipid Initiates Nerve Damage in Leprosy.

التفاصيل البيبلوغرافية
العنوان: A Macrophage Response to Mycobacterium leprae Phenolic Glycolipid Initiates Nerve Damage in Leprosy.
المؤلفون: Madigan CA; Division of Dermatology, Department of Medicine, David Geffen School of Medicine, University of California, Los Angeles, Los Angeles, CA 90095, USA; Department of Microbiology, Immunology, and Molecular Genetics, David Geffen School of Medicine, University of California, Los Angeles, Los Angeles, CA 90095, USA; Department of Microbiology, University of Washington, Seattle, WA 98195, USA. Electronic address: cmadigan@ucla.edu., Cambier CJ; Department of Immunology, University of Washington, Seattle, WA 98195, USA., Kelly-Scumpia KM; Division of Dermatology, Department of Medicine, David Geffen School of Medicine, University of California, Los Angeles, Los Angeles, CA 90095, USA., Scumpia PO; Division of Dermatology, Department of Medicine, David Geffen School of Medicine, University of California, Los Angeles, Los Angeles, CA 90095, USA., Cheng TY; Division of Rheumatology, Immunology, and Allergy, Brigham and Women's Hospital, Harvard Medical School, Boston, MA 02115, USA., Zailaa J; Department of Microbiology, Immunology, and Molecular Genetics, David Geffen School of Medicine, University of California, Los Angeles, Los Angeles, CA 90095, USA., Bloom BR; Harvard School of Public Health, Boston, MA 02115, USA., Moody DB; Division of Rheumatology, Immunology, and Allergy, Brigham and Women's Hospital, Harvard Medical School, Boston, MA 02115, USA., Smale ST; Department of Microbiology, Immunology, and Molecular Genetics, David Geffen School of Medicine, University of California, Los Angeles, Los Angeles, CA 90095, USA; Molecular Biology Institute, University of California, Los Angeles, Los Angeles, CA 90095, USA., Sagasti A; Department of Molecular, Cell, and Developmental Biology, University of California, Los Angeles, Los Angeles, CA 90095, USA., Modlin RL; Division of Dermatology, Department of Medicine, David Geffen School of Medicine, University of California, Los Angeles, Los Angeles, CA 90095, USA; Department of Microbiology, Immunology, and Molecular Genetics, David Geffen School of Medicine, University of California, Los Angeles, Los Angeles, CA 90095, USA., Ramakrishnan L; Department of Microbiology, University of Washington, Seattle, WA 98195, USA; Department of Immunology, University of Washington, Seattle, WA 98195, USA; Department of Medicine, University of Washington, Seattle, WA 98195, USA; MRC Laboratory of Molecular Biology, Molecular Immunity Unit, Department of Medicine, University of Cambridge, Cambridge CB2 OQH, UK. Electronic address: lr404@cam.ac.uk.
المصدر: Cell [Cell] 2017 Aug 24; Vol. 170 (5), pp. 973-985.e10.
نوع المنشور: Journal Article
اللغة: English
بيانات الدورية: Publisher: Cell Press Country of Publication: United States NLM ID: 0413066 Publication Model: Print Cited Medium: Internet ISSN: 1097-4172 (Electronic) Linking ISSN: 00928674 NLM ISO Abbreviation: Cell Subsets: MEDLINE
أسماء مطبوعة: Publication: Cambridge, Ma : Cell Press
Original Publication: Cambridge, MIT Press.
مواضيع طبية MeSH: Disease Models, Animal*, Antigens, Bacterial/*metabolism , Glycolipids/*metabolism , Leprosy/*microbiology , Leprosy/*pathology , Macrophages/*immunology , Mycobacterium leprae/*physiology, Animals ; Axons/metabolism ; Axons/pathology ; Demyelinating Diseases ; Larva/growth & development ; Leprosy/immunology ; Mycobacterium marinum/metabolism ; Myelin Sheath/chemistry ; Myelin Sheath/metabolism ; Myelin Sheath/ultrastructure ; Neuroglia/metabolism ; Neuroglia/pathology ; Nitric Oxide/metabolism ; Zebrafish
مستخلص: Mycobacterium leprae causes leprosy and is unique among mycobacterial diseases in producing peripheral neuropathy. This debilitating morbidity is attributed to axon demyelination resulting from direct interaction of the M. leprae-specific phenolic glycolipid 1 (PGL-1) with myelinating glia and their subsequent infection. Here, we use transparent zebrafish larvae to visualize the earliest events of M. leprae-induced nerve damage. We find that demyelination and axonal damage are not directly initiated by M. leprae but by infected macrophages that patrol axons; demyelination occurs in areas of intimate contact. PGL-1 confers this neurotoxic response on macrophages: macrophages infected with M. marinum-expressing PGL-1 also damage axons. PGL-1 induces nitric oxide synthase in infected macrophages, and the resultant increase in reactive nitrogen species damages axons by injuring their mitochondria and inducing demyelination. Our findings implicate the response of innate macrophages to M. leprae PGL-1 in initiating nerve damage in leprosy.
(Copyright © 2017 The Authors. Published by Elsevier Inc. All rights reserved.)
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Comment in: Immunity. 2017 Sep 19;47(3):395-397. (PMID: 28930653)
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معلومات مُعتمدة: R21 AI121779 United States AI NIAID NIH HHS; U19 AI111224 United States AI NIAID NIH HHS; UL1 TR000124 United States TR NCATS NIH HHS; R01 AR040312 United States AR NIAMS NIH HHS; P50 AR063020 United States AR NIAMS NIH HHS; T32 AI055396 United States AI NIAID NIH HHS; F32 AI104240 United States AI NIAID NIH HHS; UL1 TR001881 United States TR NCATS NIH HHS; R01 AI022553 United States AI NIAID NIH HHS; K08 AR066545 United States AR NIAMS NIH HHS; R01 AR064582 United States AR NIAMS NIH HHS; United Kingdom WT_ Wellcome Trust; R01 AI049313 United States AI NIAID NIH HHS; R37 AI054503 United States AI NIAID NIH HHS
فهرسة مساهمة: Keywords: leprosy; macrophage; mycobacteria; myelin; nerve damage; phenolic glycolipid; zebrafish
المشرفين على المادة: 0 (Antigens, Bacterial)
0 (Glycolipids)
0 (phenolic glycolipid I, Mycobacterium leprae)
31C4KY9ESH (Nitric Oxide)
تواريخ الأحداث: Date Created: 20170826 Date Completed: 20170901 Latest Revision: 20240402
رمز التحديث: 20240402
مُعرف محوري في PubMed: PMC5848073
DOI: 10.1016/j.cell.2017.07.030
PMID: 28841420
قاعدة البيانات: MEDLINE
الوصف
تدمد:1097-4172
DOI:10.1016/j.cell.2017.07.030