دورية أكاديمية
أعرض في EDS

Intrinsic activation of the vitamin D antimicrobial pathway by M. leprae infection is inhibited by type I IFN.

التفاصيل البيبلوغرافية
العنوان: Intrinsic activation of the vitamin D antimicrobial pathway by M. leprae infection is inhibited by type I IFN.
المؤلفون: Zavala K; UCLA/Orthopaedic Hospital, Department of Orthopaedic Surgery, David Geffen School of Medicine at UCLA, Los Angeles, California, United States of America., Gottlieb CA; UCLA/Orthopaedic Hospital, Department of Orthopaedic Surgery, David Geffen School of Medicine at UCLA, Los Angeles, California, United States of America., Teles RM; Division of Dermatology, David Geffen School of Medicine at University of California Los Angeles (UCLA), Los Angeles, California, United States of America., Adams JS; UCLA/Orthopaedic Hospital, Department of Orthopaedic Surgery, David Geffen School of Medicine at UCLA, Los Angeles, California, United States of America., Hewison M; Institute of Metabolism and Systems Research, University of Birmingham, Birmingham, United Kingdom of Great Britain and Northern Ireland., Modlin RL; Division of Dermatology, David Geffen School of Medicine at University of California Los Angeles (UCLA), Los Angeles, California, United States of America., Liu PT; UCLA/Orthopaedic Hospital, Department of Orthopaedic Surgery, David Geffen School of Medicine at UCLA, Los Angeles, California, United States of America.; Division of Dermatology, David Geffen School of Medicine at University of California Los Angeles (UCLA), Los Angeles, California, United States of America.
المصدر: PLoS neglected tropical diseases [PLoS Negl Trop Dis] 2018 Oct 09; Vol. 12 (10), pp. e0006815. Date of Electronic Publication: 2018 Oct 09 (Print Publication: 2018).
نوع المنشور: Journal Article; Research Support, N.I.H., Extramural
اللغة: English
بيانات الدورية: Publisher: Public Library of Science Country of Publication: United States NLM ID: 101291488 Publication Model: eCollection Cited Medium: Internet ISSN: 1935-2735 (Electronic) Linking ISSN: 19352727 NLM ISO Abbreviation: PLoS Negl Trop Dis Subsets: MEDLINE
أسماء مطبوعة: Original Publication: San Francisco, CA : Public Library of Science
مواضيع طبية MeSH: Immune Evasion*, Immunologic Factors/*pharmacology , Interferon Type I/*metabolism , Macrophages/*immunology , Macrophages/*microbiology , Mycobacterium leprae/*physiology , Vitamin D/*pharmacology, 25-Hydroxyvitamin D3 1-alpha-Hydroxylase/biosynthesis ; Humans ; Immunity, Innate ; Mycobacterium leprae/immunology ; Up-Regulation
مستخلص: Following infection, virulent mycobacteria persist and grow within the macrophage, suggesting that the intrinsic activation of an innate antimicrobial response is subverted by the intracellular pathogen. For Mycobacterium leprae, the intracellular bacterium that causes leprosy, the addition of exogenous innate or adaptive immune ligands to the infected monocytes/macrophages was required to detect a vitamin D-dependent antimicrobial activity. We investigated whether there is an intrinsic immune response to M. leprae in macrophages that is inhibited by the pathogen. Upon infection of monocytes with M. leprae, there was no upregulation of CYP27B1 nor its enzymatic activity converting the inactive prohormone form of vitamin D (25-hydroxyvitamin D) to the bioactive form (1,25α-dihydroxyvitamin D). Given that M. leprae-induced type I interferon (IFN) inhibited monocyte activation, we blocked the type I IFN receptor (IFNAR), revealing the intrinsic capacity of monocytes to recognize M. leprae and upregulate CYP27B1. Consistent with these in vitro studies, an inverse relationship between expression of CYP27B1 vs. type I IFN downstream gene OAS1 was detected in leprosy patient lesions, leading us to study cytokine-derived macrophages (MΦ) to model cellular responses at the site of disease. Infection of IL-15-derived MΦ, similar to MΦ in lesions from the self-limited form of leprosy, with M. leprae did not inhibit induction of the vitamin D antimicrobial pathway. In contrast, infection of IL-10-derived MΦ, similar to MΦ in lesions from patients with the progressive form of leprosy, resulted in induction of type I IFN and suppression of the vitamin D directed pathway. Importantly, blockade of the type I IFN response in infected IL-10 MΦ decreased M. leprae viability. These results indicate that M. leprae evades the intrinsic capacity of human monocytes/MΦ to activate the vitamin D-mediated antimicrobial pathway via the induction of type I IFN.
Competing Interests: The authors have declared that no competing interests exist.
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معلومات مُعتمدة: P50 AR063020 United States AR NIAMS NIH HHS; R01 AI022553 United States AI NIAID NIH HHS; R01 AR040312 United States AR NIAMS NIH HHS
المشرفين على المادة: 0 (Immunologic Factors)
0 (Interferon Type I)
1406-16-2 (Vitamin D)
EC 1.14.15.18 (25-Hydroxyvitamin D3 1-alpha-Hydroxylase)
تواريخ الأحداث: Date Created: 20181010 Date Completed: 20190109 Latest Revision: 20240314
رمز التحديث: 20240314
مُعرف محوري في PubMed: PMC6177120
DOI: 10.1371/journal.pntd.0006815
PMID: 30300363
قاعدة البيانات: MEDLINE
الوصف
تدمد:1935-2735
DOI:10.1371/journal.pntd.0006815