دورية أكاديمية
The microbiota regulates murine inflammatory responses to toxin-induced CNS demyelination but has minimal impact on remyelination.
| العنوان: | The microbiota regulates murine inflammatory responses to toxin-induced CNS demyelination but has minimal impact on remyelination. |
|---|---|
| المؤلفون: | McMurran CE; Wellcome-MRC Stem Cell Institute, University of Cambridge, CB2 0AW Cambridge, United Kingdom., Guzman de la Fuente A; Wellcome-MRC Stem Cell Institute, University of Cambridge, CB2 0AW Cambridge, United Kingdom.; Wellcome-Wolfson Institute for Experimental Medicine, Queen's University Belfast, BT9 7BL Belfast, United Kingdom., Penalva R; Wellcome-Wolfson Institute for Experimental Medicine, Queen's University Belfast, BT9 7BL Belfast, United Kingdom., Ben Menachem-Zidon O; Wellcome-MRC Stem Cell Institute, University of Cambridge, CB2 0AW Cambridge, United Kingdom.; Hadassah Human Embryonic Stem Cell Research Center, Goldyne Savad Institute of Gene Therapy, Hadassah-Hebrew University Hospital, 91240 Jerusalem, Israel., Dombrowski Y; Wellcome-Wolfson Institute for Experimental Medicine, Queen's University Belfast, BT9 7BL Belfast, United Kingdom., Falconer J; Wellcome-Wolfson Institute for Experimental Medicine, Queen's University Belfast, BT9 7BL Belfast, United Kingdom., Gonzalez GA; Wellcome-MRC Stem Cell Institute, University of Cambridge, CB2 0AW Cambridge, United Kingdom., Zhao C; Wellcome-MRC Stem Cell Institute, University of Cambridge, CB2 0AW Cambridge, United Kingdom., Krause FN; Department of Biochemistry, University of Cambridge, CB2 1GA Cambridge, United Kingdom., Young AMH; Wellcome-MRC Stem Cell Institute, University of Cambridge, CB2 0AW Cambridge, United Kingdom., Griffin JL; Department of Biochemistry, University of Cambridge, CB2 1GA Cambridge, United Kingdom., Jones CA; Respiratory, Inflammation and Autoimmunity Research, MedImmune Ltd., CB21 6GH Cambridge, United Kingdom., Hollins C; Respiratory, Inflammation and Autoimmunity Research, MedImmune Ltd., CB21 6GH Cambridge, United Kingdom., Heimesaat MM; Institute for Microbiology, Infectious Diseases and Immunology, Charité-University Medicine Berlin, 14195 Berlin, Germany., Fitzgerald DC; Wellcome-Wolfson Institute for Experimental Medicine, Queen's University Belfast, BT9 7BL Belfast, United Kingdom; d.fitzgerald@qub.ac.uk rjf1000@cam.ac.uk., Franklin RJM; Wellcome-MRC Stem Cell Institute, University of Cambridge, CB2 0AW Cambridge, United Kingdom; d.fitzgerald@qub.ac.uk rjf1000@cam.ac.uk. |
| المصدر: | Proceedings of the National Academy of Sciences of the United States of America [Proc Natl Acad Sci U S A] 2019 Dec 10; Vol. 116 (50), pp. 25311-25321. Date of Electronic Publication: 2019 Nov 18. |
| نوع المنشور: | Journal Article; Research Support, Non-U.S. Gov't |
| اللغة: | English |
| بيانات الدورية: | Publisher: National Academy of Sciences Country of Publication: United States NLM ID: 7505876 Publication Model: Print-Electronic Cited Medium: Internet ISSN: 1091-6490 (Electronic) Linking ISSN: 00278424 NLM ISO Abbreviation: Proc Natl Acad Sci U S A Subsets: MEDLINE |
| أسماء مطبوعة: | Original Publication: Washington, DC : National Academy of Sciences |
| مواضيع طبية MeSH: | Gastrointestinal Microbiome*/drug effects, Central Nervous System/*physiopathology , Multiple Sclerosis/*immunology , Multiple Sclerosis/*microbiology, Animals ; Anti-Bacterial Agents/administration & dosage ; Anti-Bacterial Agents/adverse effects ; Cell Differentiation/drug effects ; Central Nervous System/drug effects ; Central Nervous System/immunology ; Female ; Humans ; Male ; Mice ; Mice, Inbred C57BL ; Multiple Sclerosis/drug therapy ; Multiple Sclerosis/physiopathology ; Oligodendroglia/cytology ; Oligodendroglia/drug effects ; Probiotics/administration & dosage ; Remyelination/drug effects ; Stem Cells/cytology ; Stem Cells/drug effects |
| مستخلص: | The microbiota is now recognized as a key influence on the host immune response in the central nervous system (CNS). As such, there has been some progress toward therapies that modulate the microbiota with the aim of limiting immune-mediated demyelination, as occurs in multiple sclerosis. However, remyelination-the regeneration of myelin sheaths-also depends upon an immune response, and the effects that such interventions might have on remyelination have not yet been explored. Here, we show that the inflammatory response during CNS remyelination in mice is modulated by antibiotic or probiotic treatment, as well as in germ-free mice. We also explore the effect of these changes on oligodendrocyte progenitor cell differentiation, which is inhibited by antibiotics but unaffected by our other interventions. These results reveal that high combined doses of oral antibiotics impair oligodendrocyte progenitor cell responses during remyelination and further our understanding of how mammalian regeneration relates to the microbiota. Competing Interests: Competing interest statement: C.H. and C.A.J. were employed by AstraZeneca/MedImmune during the execution and interpretation of the experimental work reported here and own share/stock options in AstraZeneca. This study was, in part, sponsored by MedImmune. (Copyright © 2019 the Author(s). Published by PNAS.) |
| التعليقات: | Comment in: Proc Natl Acad Sci U S A. 2019 Dec 10;116(50):24922-24924. (PMID: 31767768) |
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| معلومات مُعتمدة: | United Kingdom WT_ Wellcome Trust; BB/N003721/1 United Kingdom BB_ Biotechnology and Biological Sciences Research Council; MR/P011705/1 United Kingdom MRC_ Medical Research Council; MC_UP_A090_1006 United Kingdom MRC_ Medical Research Council; MC_PC_13030 United Kingdom MRC_ Medical Research Council; MC_PC_12009 United Kingdom MRC_ Medical Research Council; BB/J01026X/1 United Kingdom BB_ Biotechnology and Biological Sciences Research Council; MR/P01836X/1 United Kingdom MRC_ Medical Research Council |
| فهرسة مساهمة: | Keywords: macrophage; microbiota; microglia; oligodendrocyte progenitor cell; remyelination |
| المشرفين على المادة: | 0 (Anti-Bacterial Agents) |
| تواريخ الأحداث: | Date Created: 20191120 Date Completed: 20200427 Latest Revision: 20210110 |
| رمز التحديث: | 20231215 |
| مُعرف محوري في PubMed: | PMC6911206 |
| DOI: | 10.1073/pnas.1905787116 |
| PMID: | 31740610 |
| قاعدة البيانات: | MEDLINE |
| تدمد: | 1091-6490 |
|---|---|
| DOI: | 10.1073/pnas.1905787116 |