Burkholderia pseudomallei modulates host iron homeostasis to facilitate iron availability and intracellular survival.
The control over iron homeostasis is critical in host-pathogen-interaction. Iron plays not only multiple roles for bacterial growth and pathogenicity, but also for modulation of innate immune responses. Hepcidin is a key regulator of host iron metabolism triggering degradation of the iron exporter f...
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ftdoajarticles:oai:doaj.org/article:59d1a43977cf42a99407ba32e662ee28 2023-05-15T15:12:01+02:00 Burkholderia pseudomallei modulates host iron homeostasis to facilitate iron availability and intracellular survival. Imke H E Schmidt Claudia Gildhorn Martha A L Böning Vera A Kulow Ivo Steinmetz Antje Bast 2018-01-01T00:00:00Z https://doi.org/10.1371/journal.pntd.0006096 https://doaj.org/article/59d1a43977cf42a99407ba32e662ee28 EN eng Public Library of Science (PLoS) http://europepmc.org/articles/PMC5785036?pdf=render https://doaj.org/toc/1935-2727 https://doaj.org/toc/1935-2735 1935-2727 1935-2735 doi:10.1371/journal.pntd.0006096 https://doaj.org/article/59d1a43977cf42a99407ba32e662ee28 PLoS Neglected Tropical Diseases, Vol 12, Iss 1, p e0006096 (2018) Arctic medicine. Tropical medicine RC955-962 Public aspects of medicine RA1-1270 article 2018 ftdoajarticles https://doi.org/10.1371/journal.pntd.0006096 2022-12-31T05:31:13Z The control over iron homeostasis is critical in host-pathogen-interaction. Iron plays not only multiple roles for bacterial growth and pathogenicity, but also for modulation of innate immune responses. Hepcidin is a key regulator of host iron metabolism triggering degradation of the iron exporter ferroportin. Although iron overload in humans is known to increase susceptibility to Burkholderia pseudomallei, it is unclear how the pathogen competes with the host for the metal during infection. This study aimed to investigate whether B. pseudomallei, the causative agent of melioidosis, modulates iron balance and how regulation of host cell iron content affects intracellular bacterial proliferation.Upon infection of primary macrophages with B. pseudomallei, expression of ferroportin was downregulated resulting in higher iron availability within macrophages. Exogenous modification of iron export function by hepcidin or iron supplementation by ferric ammonium citrate led to increased intracellular iron pool stimulating B. pseudomallei growth, whereas the iron chelator deferoxamine reduced bacterial survival. Iron-loaded macrophages exhibited a lower expression of NADPH oxidase, iNOS, lipocalin 2, cytokines and activation of caspase-1. Infection of mice with the pathogen caused a diminished hepatic ferroportin expression, higher iron retention in the liver and lower iron levels in the serum (hypoferremia). In vivo administration of ferric ammonium citrate tended to promote the bacterial growth and inflammatory response, whereas limitation of iron availability significantly ameliorated bacterial clearance, attenuated serum cytokine levels and improved survival of infected mice.Our data indicate that modulation of the cellular iron balance is likely to be a strategy of B. pseudomallei to improve iron acquisition and to restrict antibacterial immune effector mechanisms and thereby to promote its intracellular growth. Moreover, we provide evidence that changes in host iron homeostasis can influence susceptibility to ... Article in Journal/Newspaper Arctic Directory of Open Access Journals: DOAJ Articles Arctic PLOS Neglected Tropical Diseases 12 1 e0006096 |
institution |
Open Polar |
collection |
Directory of Open Access Journals: DOAJ Articles |
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ftdoajarticles |
language |
English |
topic |
Arctic medicine. Tropical medicine RC955-962 Public aspects of medicine RA1-1270 |
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Arctic medicine. Tropical medicine RC955-962 Public aspects of medicine RA1-1270 Imke H E Schmidt Claudia Gildhorn Martha A L Böning Vera A Kulow Ivo Steinmetz Antje Bast Burkholderia pseudomallei modulates host iron homeostasis to facilitate iron availability and intracellular survival. |
topic_facet |
Arctic medicine. Tropical medicine RC955-962 Public aspects of medicine RA1-1270 |
description |
The control over iron homeostasis is critical in host-pathogen-interaction. Iron plays not only multiple roles for bacterial growth and pathogenicity, but also for modulation of innate immune responses. Hepcidin is a key regulator of host iron metabolism triggering degradation of the iron exporter ferroportin. Although iron overload in humans is known to increase susceptibility to Burkholderia pseudomallei, it is unclear how the pathogen competes with the host for the metal during infection. This study aimed to investigate whether B. pseudomallei, the causative agent of melioidosis, modulates iron balance and how regulation of host cell iron content affects intracellular bacterial proliferation.Upon infection of primary macrophages with B. pseudomallei, expression of ferroportin was downregulated resulting in higher iron availability within macrophages. Exogenous modification of iron export function by hepcidin or iron supplementation by ferric ammonium citrate led to increased intracellular iron pool stimulating B. pseudomallei growth, whereas the iron chelator deferoxamine reduced bacterial survival. Iron-loaded macrophages exhibited a lower expression of NADPH oxidase, iNOS, lipocalin 2, cytokines and activation of caspase-1. Infection of mice with the pathogen caused a diminished hepatic ferroportin expression, higher iron retention in the liver and lower iron levels in the serum (hypoferremia). In vivo administration of ferric ammonium citrate tended to promote the bacterial growth and inflammatory response, whereas limitation of iron availability significantly ameliorated bacterial clearance, attenuated serum cytokine levels and improved survival of infected mice.Our data indicate that modulation of the cellular iron balance is likely to be a strategy of B. pseudomallei to improve iron acquisition and to restrict antibacterial immune effector mechanisms and thereby to promote its intracellular growth. Moreover, we provide evidence that changes in host iron homeostasis can influence susceptibility to ... |
format |
Article in Journal/Newspaper |
author |
Imke H E Schmidt Claudia Gildhorn Martha A L Böning Vera A Kulow Ivo Steinmetz Antje Bast |
author_facet |
Imke H E Schmidt Claudia Gildhorn Martha A L Böning Vera A Kulow Ivo Steinmetz Antje Bast |
author_sort |
Imke H E Schmidt |
title |
Burkholderia pseudomallei modulates host iron homeostasis to facilitate iron availability and intracellular survival. |
title_short |
Burkholderia pseudomallei modulates host iron homeostasis to facilitate iron availability and intracellular survival. |
title_full |
Burkholderia pseudomallei modulates host iron homeostasis to facilitate iron availability and intracellular survival. |
title_fullStr |
Burkholderia pseudomallei modulates host iron homeostasis to facilitate iron availability and intracellular survival. |
title_full_unstemmed |
Burkholderia pseudomallei modulates host iron homeostasis to facilitate iron availability and intracellular survival. |
title_sort |
burkholderia pseudomallei modulates host iron homeostasis to facilitate iron availability and intracellular survival. |
publisher |
Public Library of Science (PLoS) |
publishDate |
2018 |
url |
https://doi.org/10.1371/journal.pntd.0006096 https://doaj.org/article/59d1a43977cf42a99407ba32e662ee28 |
geographic |
Arctic |
geographic_facet |
Arctic |
genre |
Arctic |
genre_facet |
Arctic |
op_source |
PLoS Neglected Tropical Diseases, Vol 12, Iss 1, p e0006096 (2018) |
op_relation |
http://europepmc.org/articles/PMC5785036?pdf=render https://doaj.org/toc/1935-2727 https://doaj.org/toc/1935-2735 1935-2727 1935-2735 doi:10.1371/journal.pntd.0006096 https://doaj.org/article/59d1a43977cf42a99407ba32e662ee28 |
op_doi |
https://doi.org/10.1371/journal.pntd.0006096 |
container_title |
PLOS Neglected Tropical Diseases |
container_volume |
12 |
container_issue |
1 |
container_start_page |
e0006096 |
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1766342777559318528 |