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Chlamydophila pneumoniae changes iron homeostasis in infected tissues
Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Infectious Diseases.
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2008 (English)In: International Journal of Medical Microbiology, ISSN 1438-4221, Vol. 298, no 7-8, 635-44 p.Article in journal (Refereed) Published
Abstract [en]

Many bacteria, including Chlamydophila pneumoniae (C. pneumoniae), are dependent on iron (Fe) for their growth. However, it is not known whether bacterial infections affect gastrointestinal uptake and uptake of trace elements in infected tissues. A human C. pneumoniae strain adapted to C57BL/6J mice was used to study hepcidin gene expression in the liver and divalent metal transporter 1 (DMT1) content in the liver and intestine and whether Fe is concomitantly changed in serum, liver, and intestine. The copper/zinc (Cu/Zn) ratio in the serum was used as a marker for infection. Bacterial DNA, mRNA, and hepcidin were measured by real-time PCR, DMT1 by Western blot, and trace elements by ICP-MS on days 2, 5, and 8 of the infection. C. pneumoniae DNA was found in the liver on all days but the number of viable bacteria peaked on day 8. Hepcidin expression increased on days 2 and 5, whereas DMT1 content in the liver increased on day 8. Fe decreased in serum, increased in the liver but was not changed in the intestine during the disease. In the serum, the Cu/Zn ratio peaked on day 5. The peak of viable bacteria in the liver was associated with increased DMT1 and Fe contents and increased hepcidin expression, but this did not affect intestinal Fe uptake. Thus, growth of C. pneumoniae in tissues parallels a redistribution of Fe to those tissues resulting in a changed body homeostasis of Fe.

Place, publisher, year, edition, pages
2008. Vol. 298, no 7-8, 635-44 p.
Keyword [en]
Chlamydophila pneumoniae, Chlamydia pneumoniae, DMT1, Hepcidin, Iron, Liver
National Category
Medical and Health Sciences
URN: urn:nbn:se:uu:diva-97119DOI: 10.1016/j.ijmm.2008.01.014ISI: 000260142400009PubMedID: 18436480OAI: oai:DiVA.org:uu-97119DiVA: diva2:171917
Available from: 2008-04-25 Created: 2008-04-25 Last updated: 2009-07-16Bibliographically approved
In thesis
1. Chlamydophila pneumoniae in Cardiovascular Diseases: Clinical and Experimental Studies
Open this publication in new window or tab >>Chlamydophila pneumoniae in Cardiovascular Diseases: Clinical and Experimental Studies
2008 (English)Doctoral thesis, comprehensive summary (Other academic)
Abstract [en]

Chlamydophila pneumoniae (C. pneumoniae) has been suggested as a stimulator of chronic inflammation in atherosclerosis. C. pneumoniae DNA was demonstrated in aortic biopsies in 50% of patients with stable angina pectoris or acute coronary syndrome undergoing coronary artery bypass grafting. C. pneumoniae mRNA, a marker of replicating bacteria, was demonstrated in 18% of the aortic biopsies.

Inflammation may have a role in the pathogenesis of thoracic aortic aneurysm, aortic dissection and aortic valve stenosis. C. pneumoniae DNA was demonstrated in aortic biopsies in 26% of thoracic aortic aneurysm patients and in 11% of aortic dissection patients undergoing thoracic surgery and in 22% of stenotic aortic heart valves from patients undergoing aortic valve replacement. No bacterial mRNA was demonstrated in these aortic biopsies, nor in the valves, suggesting that the infection has passed into a persistent state. C. pneumoniae DNA was demonstrated in peripheral blood mononuclear cells in only 5% of aortic valve stenosis patients and not in thoracic aortic aneurysm or aortic dissection patients, suggesting that the bacterium disseminated to the cardiovascular tissue long before the patient required surgery. The copper/zinc ratio in serum, a marker of infection/inflammation, was significantly elevated in thoracic aortic aneurysm patients, supporting an inflammatory pathogenesis. Patients positive for C. pneumoniae in the aortic valve had more advanced coronary atherosclerosis, further supporting a possible role for C. pneumoniae in atherosclerosis.

Mice were infected with C. pneumoniae that disseminated to all organs investigated (i.e. lungs, heart, aorta, liver and spleen). Trace element concentrations were altered in infected animals with an increased copper/zinc ratio in serum, a progressively increased iron concentration in the liver and a progressively decreased iron concentration in serum. Iron is important for C. pneumoniae metabolism, and a changed iron homeostasis was noted in infected mice by alterations in iron-regulating proteins, such as DMT1 and hepcidin.

Place, publisher, year, edition, pages
Uppsala: Acta Universitatis Upsaliensis, 2008. 71 p.
Digital Comprehensive Summaries of Uppsala Dissertations from the Faculty of Medicine, ISSN 1651-6206 ; 340
Communicable diseases, Chlamydophila pneumoniae, Chlamydia pneumoniae, trace elements, atherosclerosis, aortic valve stenosis, thoracic aortic aneurysm, aortic dissection, hepcidin, iron, Infektionssjukdomar
urn:nbn:se:uu:diva-8667 (URN)978-91-554-7176-7 (ISBN)
Public defence
2008-05-23, Hörsalen, Akademiska sjukhuset, ing. D1, Dag Hammarsköldsväg 17, Uppsala, 09:15
Available from: 2008-04-25 Created: 2008-04-25Bibliographically approved

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