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...

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Autores principales:	Rodrigo Abreu, Lauren Essler, Allyson Loy, Frederick Quinn, Pramod Giri
Formato:	article
Lenguaje:	EN
Publicado:	Nature Portfolio 2018
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/8d2b790173db44289b522a6156c41789
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spelling	oai:doaj.org-article:8d2b790173db44289b522a6156c417892021-12-02T12:32:09ZHeparin inhibits intracellular Mycobacterium tuberculosis bacterial replication by reducing iron levels in human macrophages10.1038/s41598-018-25480-y2045-2322https://doaj.org/article/8d2b790173db44289b522a6156c417892018-05-01T00:00:00Zhttps://doi.org/10.1038/s41598-018-25480-yhttps://doaj.org/toc/2045-2322Abstract 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.Rodrigo AbreuLauren EsslerAllyson LoyFrederick QuinnPramod GiriNature PortfolioarticleMedicineRScienceQENScientific Reports, Vol 8, Iss 1, Pp 1-12 (2018)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Rodrigo Abreu Lauren Essler Allyson Loy Frederick Quinn Pramod Giri Heparin inhibits intracellular Mycobacterium tuberculosis bacterial replication by reducing iron levels in human macrophages
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.
format	article
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
title	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_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_sort	heparin inhibits intracellular mycobacterium tuberculosis bacterial replication by reducing iron levels in human macrophages
publisher	Nature Portfolio
publishDate	2018
url	https://doaj.org/article/8d2b790173db44289b522a6156c41789
work_keys_str_mv	AT rodrigoabreu heparininhibitsintracellularmycobacteriumtuberculosisbacterialreplicationbyreducingironlevelsinhumanmacrophages AT laurenessler heparininhibitsintracellularmycobacteriumtuberculosisbacterialreplicationbyreducingironlevelsinhumanmacrophages AT allysonloy heparininhibitsintracellularmycobacteriumtuberculosisbacterialreplicationbyreducingironlevelsinhumanmacrophages AT frederickquinn heparininhibitsintracellularmycobacteriumtuberculosisbacterialreplicationbyreducingironlevelsinhumanmacrophages AT pramodgiri heparininhibitsintracellularmycobacteriumtuberculosisbacterialreplicationbyreducingironlevelsinhumanmacrophages
_version_	1718394170870071296

Heparin inhibits intracellular Mycobacterium tuberculosis bacterial replication by reducing iron levels in human macrophages

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