Fenofibrate Facilitates Post-Active Tuberculosis Infection in Macrophages and is Associated with Higher Mortality in Patients under Long-Term Treatment
Background: <i>Mycobacterium tuberculosis</i> (<i>Mtb</i>) is an intracellular pathogen that infects and persists in macrophages. This study aimed to investigate the effects of long-term fenofibrate treatment in patients with tuberculosis (TB), and the intracellular viability...
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doaj-3f5c0f916c0c4241820bbe8ac62d44112020-11-25T02:20:25ZengMDPI AGJournal of Clinical Medicine2077-03832020-01-019233710.3390/jcm9020337jcm9020337Fenofibrate Facilitates Post-Active Tuberculosis Infection in Macrophages and is Associated with Higher Mortality in Patients under Long-Term TreatmentChing-Lung Liu0Yen-Ta Lu1I-Fan Tsai2Ling-Chiao Wu3Wu-Chien Chien4Chi-Hsiang Chung5Kuo-Hsing Ma6Division of Chest Medicine, Department of Internal Medicine, MacKay Memorial Hospital, Taipei 104, TaiwanDivision of Chest Medicine, Department of Internal Medicine, MacKay Memorial Hospital, Taipei 104, TaiwanDepartment of Medical Research, MacKay Memorial Hospital, Taipei 104, TaiwanDepartment of Medical Research, MacKay Memorial Hospital, Taipei 104, TaiwanDepartment of Medical Research, National Defense Medical Center, Taipei 114, TaiwanSchool of Public Health, National Defense Medical Center, Taipei 114, TaiwanDepartment of Biology and Anatomy, National Defense Medical Center, Taipei 114, TaiwanBackground: <i>Mycobacterium tuberculosis</i> (<i>Mtb</i>) is an intracellular pathogen that infects and persists in macrophages. This study aimed to investigate the effects of long-term fenofibrate treatment in patients with tuberculosis (TB), and the intracellular viability of <i>Mtb</i> in human macrophages. Methods: Epidemiological data from the National Health Insurance Research Database of Taiwan were used to present outcomes of TB patients treated with fenofibrate. In the laboratory, we assessed <i>Mtb</i> infection in macrophages treated with or without fenofibrate. <i>Mtb</i> growth, lipid accumulation in macrophages, and expression of transcriptional genes were examined. Results: During 11 years of follow-up, TB patients treated with fenofibrate presented a higher risk of mortality. Longer duration of fenofibrate use was associated with a significantly higher risk of mortality. Treatment with fenofibrate significantly increased the number of bacilli in human macrophages in vitro. Fenofibrate did not reduce, but induced an increasing trend in the intracellular lipid content of macrophages. In addition, dormant genes of <i>Mtb</i>, <i>icl1</i>, <i>tgs1</i>, and <i>devR</i>, were markedly upregulated in response to fenofibrate treatment. Our results suggest that fenofibrate may facilitate intracellular <i>Mtb</i> persistence. Conclusions: Our data shows that long-term treatment with fenofibrate in TB patients is associated with a higher mortality. The underlying mechanisms may partly be explained by the upregulation of <i>Mtb</i> genes involved in lipid metabolism, enhanced intracellular growth of <i>Mtb</i>, and the ability of <i>Mtb</i> to sustain a nutrient-rich reservoir in human macrophages, observed during treatment with fenofibrate.https://www.mdpi.com/2077-0383/9/2/337fenofibratetuberculosis infectionlipidmycobacterial tuberculosis |
collection |
DOAJ |
language |
English |
format |
Article |
sources |
DOAJ |
author |
Ching-Lung Liu Yen-Ta Lu I-Fan Tsai Ling-Chiao Wu Wu-Chien Chien Chi-Hsiang Chung Kuo-Hsing Ma |
spellingShingle |
Ching-Lung Liu Yen-Ta Lu I-Fan Tsai Ling-Chiao Wu Wu-Chien Chien Chi-Hsiang Chung Kuo-Hsing Ma Fenofibrate Facilitates Post-Active Tuberculosis Infection in Macrophages and is Associated with Higher Mortality in Patients under Long-Term Treatment Journal of Clinical Medicine fenofibrate tuberculosis infection lipid mycobacterial tuberculosis |
author_facet |
Ching-Lung Liu Yen-Ta Lu I-Fan Tsai Ling-Chiao Wu Wu-Chien Chien Chi-Hsiang Chung Kuo-Hsing Ma |
author_sort |
Ching-Lung Liu |
title |
Fenofibrate Facilitates Post-Active Tuberculosis Infection in Macrophages and is Associated with Higher Mortality in Patients under Long-Term Treatment |
title_short |
Fenofibrate Facilitates Post-Active Tuberculosis Infection in Macrophages and is Associated with Higher Mortality in Patients under Long-Term Treatment |
title_full |
Fenofibrate Facilitates Post-Active Tuberculosis Infection in Macrophages and is Associated with Higher Mortality in Patients under Long-Term Treatment |
title_fullStr |
Fenofibrate Facilitates Post-Active Tuberculosis Infection in Macrophages and is Associated with Higher Mortality in Patients under Long-Term Treatment |
title_full_unstemmed |
Fenofibrate Facilitates Post-Active Tuberculosis Infection in Macrophages and is Associated with Higher Mortality in Patients under Long-Term Treatment |
title_sort |
fenofibrate facilitates post-active tuberculosis infection in macrophages and is associated with higher mortality in patients under long-term treatment |
publisher |
MDPI AG |
series |
Journal of Clinical Medicine |
issn |
2077-0383 |
publishDate |
2020-01-01 |
description |
Background: <i>Mycobacterium tuberculosis</i> (<i>Mtb</i>) is an intracellular pathogen that infects and persists in macrophages. This study aimed to investigate the effects of long-term fenofibrate treatment in patients with tuberculosis (TB), and the intracellular viability of <i>Mtb</i> in human macrophages. Methods: Epidemiological data from the National Health Insurance Research Database of Taiwan were used to present outcomes of TB patients treated with fenofibrate. In the laboratory, we assessed <i>Mtb</i> infection in macrophages treated with or without fenofibrate. <i>Mtb</i> growth, lipid accumulation in macrophages, and expression of transcriptional genes were examined. Results: During 11 years of follow-up, TB patients treated with fenofibrate presented a higher risk of mortality. Longer duration of fenofibrate use was associated with a significantly higher risk of mortality. Treatment with fenofibrate significantly increased the number of bacilli in human macrophages in vitro. Fenofibrate did not reduce, but induced an increasing trend in the intracellular lipid content of macrophages. In addition, dormant genes of <i>Mtb</i>, <i>icl1</i>, <i>tgs1</i>, and <i>devR</i>, were markedly upregulated in response to fenofibrate treatment. Our results suggest that fenofibrate may facilitate intracellular <i>Mtb</i> persistence. Conclusions: Our data shows that long-term treatment with fenofibrate in TB patients is associated with a higher mortality. The underlying mechanisms may partly be explained by the upregulation of <i>Mtb</i> genes involved in lipid metabolism, enhanced intracellular growth of <i>Mtb</i>, and the ability of <i>Mtb</i> to sustain a nutrient-rich reservoir in human macrophages, observed during treatment with fenofibrate. |
topic |
fenofibrate tuberculosis infection lipid mycobacterial tuberculosis |
url |
https://www.mdpi.com/2077-0383/9/2/337 |
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