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RETRACTED ARTICLE: Ornithine-A urea cycle metabolite enhances autophagy and controls Mycobacterium tuberculosis infection
Macrophages are professional phagocytes known to play a vital role in controlling Mycobacterium tuberculosis (Mtb) infection and disease progression. Here we compare Mtb growth in mouse alveolar (AMs), peritoneal (PMs), and liver (Kupffer cells; KCs) macrophages and in bone marrow-derived monocytes...
Autores principales: | , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Nature Publishing Group UK
2020
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7363810/ https://www.ncbi.nlm.nih.gov/pubmed/32669568 http://dx.doi.org/10.1038/s41467-020-17310-5 |
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author | Sivangala Thandi, Ramya Radhakrishnan, Rajesh Kumar Tripathi, Deepak Paidipally, Padmaja Azad, Abul K. Schlesinger, Larry S. Samten, Buka Mulik, Sachin Vankayalapati, Ramakrishna |
author_facet | Sivangala Thandi, Ramya Radhakrishnan, Rajesh Kumar Tripathi, Deepak Paidipally, Padmaja Azad, Abul K. Schlesinger, Larry S. Samten, Buka Mulik, Sachin Vankayalapati, Ramakrishna |
author_sort | Sivangala Thandi, Ramya |
collection | PubMed |
description | Macrophages are professional phagocytes known to play a vital role in controlling Mycobacterium tuberculosis (Mtb) infection and disease progression. Here we compare Mtb growth in mouse alveolar (AMs), peritoneal (PMs), and liver (Kupffer cells; KCs) macrophages and in bone marrow-derived monocytes (BDMs). KCs restrict Mtb growth more efficiently than all other macrophages and monocytes despite equivalent infections through enhanced autophagy. A metabolomics comparison of Mtb-infected macrophages indicates that ornithine and imidazole are two top-scoring metabolites in Mtb-infected KCs and that acetylcholine is the top-scoring in Mtb-infected AMs. Ornithine, imidazole and atropine (acetylcholine inhibitor) inhibit Mtb growth in AMs. Ornithine enhances AMPK mediated autophagy whereas imidazole directly kills Mtb by reducing cytochrome P450 activity. Intranasal delivery of ornithine or imidazole or the two together restricts Mtb growth. Our study demonstrates that the metabolic differences between Mtb-infected AMs and KCs lead to differences in the restriction of Mtb growth. |
format | Online Article Text |
id | pubmed-7363810 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2020 |
publisher | Nature Publishing Group UK |
record_format | MEDLINE/PubMed |
spelling | pubmed-73638102020-07-20 RETRACTED ARTICLE: Ornithine-A urea cycle metabolite enhances autophagy and controls Mycobacterium tuberculosis infection Sivangala Thandi, Ramya Radhakrishnan, Rajesh Kumar Tripathi, Deepak Paidipally, Padmaja Azad, Abul K. Schlesinger, Larry S. Samten, Buka Mulik, Sachin Vankayalapati, Ramakrishna Nat Commun Article Macrophages are professional phagocytes known to play a vital role in controlling Mycobacterium tuberculosis (Mtb) infection and disease progression. Here we compare Mtb growth in mouse alveolar (AMs), peritoneal (PMs), and liver (Kupffer cells; KCs) macrophages and in bone marrow-derived monocytes (BDMs). KCs restrict Mtb growth more efficiently than all other macrophages and monocytes despite equivalent infections through enhanced autophagy. A metabolomics comparison of Mtb-infected macrophages indicates that ornithine and imidazole are two top-scoring metabolites in Mtb-infected KCs and that acetylcholine is the top-scoring in Mtb-infected AMs. Ornithine, imidazole and atropine (acetylcholine inhibitor) inhibit Mtb growth in AMs. Ornithine enhances AMPK mediated autophagy whereas imidazole directly kills Mtb by reducing cytochrome P450 activity. Intranasal delivery of ornithine or imidazole or the two together restricts Mtb growth. Our study demonstrates that the metabolic differences between Mtb-infected AMs and KCs lead to differences in the restriction of Mtb growth. Nature Publishing Group UK 2020-07-15 /pmc/articles/PMC7363810/ /pubmed/32669568 http://dx.doi.org/10.1038/s41467-020-17310-5 Text en © The Author(s) 2020 https://creativecommons.org/licenses/by/4.0/Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/ (https://creativecommons.org/licenses/by/4.0/) . |
spellingShingle | Article Sivangala Thandi, Ramya Radhakrishnan, Rajesh Kumar Tripathi, Deepak Paidipally, Padmaja Azad, Abul K. Schlesinger, Larry S. Samten, Buka Mulik, Sachin Vankayalapati, Ramakrishna RETRACTED ARTICLE: Ornithine-A urea cycle metabolite enhances autophagy and controls Mycobacterium tuberculosis infection |
title | RETRACTED ARTICLE: Ornithine-A urea cycle metabolite enhances autophagy and controls Mycobacterium tuberculosis infection |
title_full | RETRACTED ARTICLE: Ornithine-A urea cycle metabolite enhances autophagy and controls Mycobacterium tuberculosis infection |
title_fullStr | RETRACTED ARTICLE: Ornithine-A urea cycle metabolite enhances autophagy and controls Mycobacterium tuberculosis infection |
title_full_unstemmed | RETRACTED ARTICLE: Ornithine-A urea cycle metabolite enhances autophagy and controls Mycobacterium tuberculosis infection |
title_short | RETRACTED ARTICLE: Ornithine-A urea cycle metabolite enhances autophagy and controls Mycobacterium tuberculosis infection |
title_sort | retracted article: ornithine-a urea cycle metabolite enhances autophagy and controls mycobacterium tuberculosis infection |
topic | Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7363810/ https://www.ncbi.nlm.nih.gov/pubmed/32669568 http://dx.doi.org/10.1038/s41467-020-17310-5 |
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