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Hepcidin deficiency and iron deficiency do not alter tuberculosis susceptibility in a murine M.tb infection model
Tuberculosis (TB), caused by the macrophage-tropic pathogen Mycobacterium tuberculosis (M.tb) is a highly prevalent infectious disease. Since an immune correlate of protection or effective vaccine have yet to be found, continued research into host-pathogen interactions is important. Previous literat...
Autores principales: | , , , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Public Library of Science
2018
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5764373/ https://www.ncbi.nlm.nih.gov/pubmed/29324800 http://dx.doi.org/10.1371/journal.pone.0191038 |
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author | Harrington-Kandt, Rachel Stylianou, Elena Eddowes, Lucy A. Lim, Pei Jin Stockdale, Lisa Pinpathomrat, Nawamin Bull, Naomi Pasricha, Janet Ulaszewska, Marta Beglov, Yulia Vaulont, Sophie Drakesmith, Hal McShane, Helen |
author_facet | Harrington-Kandt, Rachel Stylianou, Elena Eddowes, Lucy A. Lim, Pei Jin Stockdale, Lisa Pinpathomrat, Nawamin Bull, Naomi Pasricha, Janet Ulaszewska, Marta Beglov, Yulia Vaulont, Sophie Drakesmith, Hal McShane, Helen |
author_sort | Harrington-Kandt, Rachel |
collection | PubMed |
description | Tuberculosis (TB), caused by the macrophage-tropic pathogen Mycobacterium tuberculosis (M.tb) is a highly prevalent infectious disease. Since an immune correlate of protection or effective vaccine have yet to be found, continued research into host-pathogen interactions is important. Previous literature reports links between host iron status and disease outcome for many infections, including TB. For some extracellular bacteria, the iron regulatory hormone hepcidin is essential for protection against infection. Here, we investigated hepcidin (encoded by Hamp1) in the context of murine M.tb infection. Female C57BL/6 mice were infected with M.tb Erdman via aerosol. Hepatic expression of iron-responsive genes was measured by qRT-PCR and bacterial burden determined in organ homogenates. We found that hepatic Hamp1 mRNA levels decreased post-infection, and correlated with a marker of BMP/SMAD signalling pathways. Next, we tested the effect of Hamp1 deletion, and low iron diets, on M.tb infection. Hamp1 knockout mice did not have a significantly altered M.tb mycobacterial load in either the lungs or spleen. Up to 10 weeks of dietary iron restriction did not robustly affect disease outcome despite causing iron deficiency anaemia. Taken together, our data indicate that unlike with many other infections, hepcidin is decreased following M.tb infection, and show that hepcidin ablation does not influence M.tb growth in vivo. Furthermore, because even severe iron deficiency did not affect M.tb mycobacterial load, we suggest that the mechanisms M.tb uses to scavenge iron from the host must be extremely efficient, and may therefore represent potential targets for drugs and vaccines. |
format | Online Article Text |
id | pubmed-5764373 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2018 |
publisher | Public Library of Science |
record_format | MEDLINE/PubMed |
spelling | pubmed-57643732018-01-23 Hepcidin deficiency and iron deficiency do not alter tuberculosis susceptibility in a murine M.tb infection model Harrington-Kandt, Rachel Stylianou, Elena Eddowes, Lucy A. Lim, Pei Jin Stockdale, Lisa Pinpathomrat, Nawamin Bull, Naomi Pasricha, Janet Ulaszewska, Marta Beglov, Yulia Vaulont, Sophie Drakesmith, Hal McShane, Helen PLoS One Research Article Tuberculosis (TB), caused by the macrophage-tropic pathogen Mycobacterium tuberculosis (M.tb) is a highly prevalent infectious disease. Since an immune correlate of protection or effective vaccine have yet to be found, continued research into host-pathogen interactions is important. Previous literature reports links between host iron status and disease outcome for many infections, including TB. For some extracellular bacteria, the iron regulatory hormone hepcidin is essential for protection against infection. Here, we investigated hepcidin (encoded by Hamp1) in the context of murine M.tb infection. Female C57BL/6 mice were infected with M.tb Erdman via aerosol. Hepatic expression of iron-responsive genes was measured by qRT-PCR and bacterial burden determined in organ homogenates. We found that hepatic Hamp1 mRNA levels decreased post-infection, and correlated with a marker of BMP/SMAD signalling pathways. Next, we tested the effect of Hamp1 deletion, and low iron diets, on M.tb infection. Hamp1 knockout mice did not have a significantly altered M.tb mycobacterial load in either the lungs or spleen. Up to 10 weeks of dietary iron restriction did not robustly affect disease outcome despite causing iron deficiency anaemia. Taken together, our data indicate that unlike with many other infections, hepcidin is decreased following M.tb infection, and show that hepcidin ablation does not influence M.tb growth in vivo. Furthermore, because even severe iron deficiency did not affect M.tb mycobacterial load, we suggest that the mechanisms M.tb uses to scavenge iron from the host must be extremely efficient, and may therefore represent potential targets for drugs and vaccines. Public Library of Science 2018-01-11 /pmc/articles/PMC5764373/ /pubmed/29324800 http://dx.doi.org/10.1371/journal.pone.0191038 Text en © 2018 Harrington-Kandt et al http://creativecommons.org/licenses/by/4.0/ This is an open access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/4.0/) , which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited. |
spellingShingle | Research Article Harrington-Kandt, Rachel Stylianou, Elena Eddowes, Lucy A. Lim, Pei Jin Stockdale, Lisa Pinpathomrat, Nawamin Bull, Naomi Pasricha, Janet Ulaszewska, Marta Beglov, Yulia Vaulont, Sophie Drakesmith, Hal McShane, Helen Hepcidin deficiency and iron deficiency do not alter tuberculosis susceptibility in a murine M.tb infection model |
title | Hepcidin deficiency and iron deficiency do not alter tuberculosis susceptibility in a murine M.tb infection model |
title_full | Hepcidin deficiency and iron deficiency do not alter tuberculosis susceptibility in a murine M.tb infection model |
title_fullStr | Hepcidin deficiency and iron deficiency do not alter tuberculosis susceptibility in a murine M.tb infection model |
title_full_unstemmed | Hepcidin deficiency and iron deficiency do not alter tuberculosis susceptibility in a murine M.tb infection model |
title_short | Hepcidin deficiency and iron deficiency do not alter tuberculosis susceptibility in a murine M.tb infection model |
title_sort | hepcidin deficiency and iron deficiency do not alter tuberculosis susceptibility in a murine m.tb infection model |
topic | Research Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5764373/ https://www.ncbi.nlm.nih.gov/pubmed/29324800 http://dx.doi.org/10.1371/journal.pone.0191038 |
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