Heparin inhibits intracellular Mycobacterium tuberculosis bacterial replication by reducing iron levels in human macrophages
Abstract Iron is a crucial micronutrient for both mammals and their associated pathogens, and extensive literature has shown that Mycobacterium tuberculosis (Mtb) bacilli inhibited from acquiring iron from the host are severely attenuated. In contrast, increased dietary iron concentrations or patien...
| Main Authors: | , , , , |
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| Format: | Article |
| Language: | English |
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Nature Portfolio
2018-05-01
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| Series: | Scientific Reports |
| Online Access: | https://doi.org/10.1038/s41598-018-25480-y |
| _version_ | 1818405761570570240 |
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| author | Rodrigo Abreu Lauren Essler Allyson Loy Frederick Quinn Pramod Giri |
| author_facet | Rodrigo Abreu Lauren Essler Allyson Loy Frederick Quinn Pramod Giri |
| author_sort | Rodrigo Abreu |
| collection | DOAJ |
| description | Abstract Iron is a crucial micronutrient for both mammals and their associated pathogens, and extensive literature has shown that Mycobacterium tuberculosis (Mtb) bacilli inhibited from acquiring iron from the host are severely attenuated. In contrast, increased dietary iron concentrations or patients with hemochromatosis have long been associated with a more severe tuberculosis (TB) disease outcome. We have observed that upon macrophage infection, Mtb bacilli strongly promote intracellular iron sequestration, both through increased expression of hepcidin, a key mammalian iron regulatory protein, and downregulation of the iron exporter protein, ferroportin. Heparin is a highly sulfated glycosaminoglycan released by mast cells and basophils at sites of tissue injury. During Mtb infection, heparin alters intracellular trafficking in alveolar epithelial cells and decreases extrapulmonary dissemination but recently, heparin also has been reported to inhibit hepcidin expression in hepatocytes, decreasing intracellular iron availability. In this report, we demonstrate that heparin significantly reduces hepcidin expression in macrophages infected with Mtb bacilli. Heparin-treated macrophages have higher ferroportin expression compared to untreated macrophages, promoting iron export and decreasing iron availability to intracellular bacilli. Thus, here we describe a novel immunomodulatory effect and potential therapeutic role for heparin against mycobacterial infection in human macrophages. |
| first_indexed | 2024-12-14T09:01:11Z |
| format | Article |
| id | doaj.art-8d2b790173db44289b522a6156c41789 |
| institution | Directory Open Access Journal |
| issn | 2045-2322 |
| language | English |
| last_indexed | 2024-12-14T09:01:11Z |
| publishDate | 2018-05-01 |
| publisher | Nature Portfolio |
| record_format | Article |
| series | Scientific Reports |
| spelling | doaj.art-8d2b790173db44289b522a6156c417892022-12-21T23:08:49ZengNature PortfolioScientific Reports2045-23222018-05-018111210.1038/s41598-018-25480-yHeparin inhibits intracellular Mycobacterium tuberculosis bacterial replication by reducing iron levels in human macrophagesRodrigo Abreu0Lauren Essler1Allyson Loy2Frederick Quinn3Pramod Giri4Department of Infectious Diseases, College of Veterinary Medicine, University of GeorgiaDepartment of Infectious Diseases, College of Veterinary Medicine, University of GeorgiaDepartment of Infectious Diseases, College of Veterinary Medicine, University of GeorgiaDepartment of Infectious Diseases, College of Veterinary Medicine, University of GeorgiaDepartment of Infectious Diseases, College of Veterinary Medicine, University of GeorgiaAbstract Iron is a crucial micronutrient for both mammals and their associated pathogens, and extensive literature has shown that Mycobacterium tuberculosis (Mtb) bacilli inhibited from acquiring iron from the host are severely attenuated. In contrast, increased dietary iron concentrations or patients with hemochromatosis have long been associated with a more severe tuberculosis (TB) disease outcome. We have observed that upon macrophage infection, Mtb bacilli strongly promote intracellular iron sequestration, both through increased expression of hepcidin, a key mammalian iron regulatory protein, and downregulation of the iron exporter protein, ferroportin. Heparin is a highly sulfated glycosaminoglycan released by mast cells and basophils at sites of tissue injury. During Mtb infection, heparin alters intracellular trafficking in alveolar epithelial cells and decreases extrapulmonary dissemination but recently, heparin also has been reported to inhibit hepcidin expression in hepatocytes, decreasing intracellular iron availability. In this report, we demonstrate that heparin significantly reduces hepcidin expression in macrophages infected with Mtb bacilli. Heparin-treated macrophages have higher ferroportin expression compared to untreated macrophages, promoting iron export and decreasing iron availability to intracellular bacilli. Thus, here we describe a novel immunomodulatory effect and potential therapeutic role for heparin against mycobacterial infection in human macrophages.https://doi.org/10.1038/s41598-018-25480-y |
| spellingShingle | Rodrigo Abreu Lauren Essler Allyson Loy Frederick Quinn Pramod Giri Heparin inhibits intracellular Mycobacterium tuberculosis bacterial replication by reducing iron levels in human macrophages Scientific Reports |
| title | Heparin inhibits intracellular Mycobacterium tuberculosis bacterial replication by reducing iron levels in human macrophages |
| title_full | Heparin inhibits intracellular Mycobacterium tuberculosis bacterial replication by reducing iron levels in human macrophages |
| title_fullStr | Heparin inhibits intracellular Mycobacterium tuberculosis bacterial replication by reducing iron levels in human macrophages |
| title_full_unstemmed | Heparin inhibits intracellular Mycobacterium tuberculosis bacterial replication by reducing iron levels in human macrophages |
| title_short | Heparin inhibits intracellular Mycobacterium tuberculosis bacterial replication by reducing iron levels in human macrophages |
| title_sort | heparin inhibits intracellular mycobacterium tuberculosis bacterial replication by reducing iron levels in human macrophages |
| url | https://doi.org/10.1038/s41598-018-25480-y |
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