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Increased Iron Stores Correlate with Worse Disease Outcomes in a Mouse
Model of Schistosomiasis Infection
Cameron J. McDonald1, Malcolm K. Jones2,3, Daniel F. Wallace1, Lesa
Summerville1, Sujeevi Nawaratna2,3, V. Nathan Subramaniam1,4*
1 Membrane Transport Laboratory, Division of Cancer and Cell Biology,
Queensland Institute of Medical Research, Brisbane, Queensland,
Australia, 2 Parasite Cell Biology Laboratory, Division of Infectious
Diseases and Immunology, Queensland Institute of Medical Research,
Brisbane, Queensland, Australia, 3 School of Veterinary Science, The
University of Queensland, Brisbane, Queensland, Australia, 4 Liver
Research Centre, School of Medicine, The University of Queensland,
Brisbane, Queensland, Australia

Abstract Top
Schistosomiasis is a significant parasitic infection creating disease
burden throughout many of the world's developing nations.
Iron deficiency anemia is also a significant health burden resulting
from both nutritional deficit as well as parasitic infection in these
countries.
In this study we investigated the relationships between the disease
outcomes of Schistosoma japonicum infection and iron homeostasis.
We aimed to determine if host iron status has an effect on schistosome
maturation or egg production, and to investigate the response of iron
regulatory genes to chronic schistosomiasis infection.
Wild-type C57BL/6 and Transferrin Receptor 2 null mice were infected
with S. japonicum, and sacrificed at the onset of chronic disease.
Transferrin Receptor 2 null mice are a model of type 3 hereditary
hemochromatosis and develop significant iron overload providing
increased iron stores at the onset of infection.
The infectivity of schistosomes and egg production was assessed along
with the subsequent development of granulomas and fibrosis.
The response of the iron regulatory gene Hepcidin to infection and the
changes in iron status were assessed by real-time PCR and Western
blotting.
Our results show that Hepcidin levels responded to the changing iron
status of the animals, but were not significantly influenced by the
inflammatory response.
We also show that with increased iron availability at the time of
infection there was greater development of fibrosis around
granulomas.
In conclusion, our studies indicate that chronic inflammation may not
be the primary cause of the anemia seen in schistosomiasis, and
suggest that increased availability of iron, such as through iron
supplementation, may actually lead to increased disease severity.

Citation: McDonald CJ, Jones MK, Wallace DF, Summerville L, Nawaratna
S, et al. (2010) Increased Iron Stores Correlate with Worse Disease
Outcomes in a Mouse Model of Schistosomiasis Infection. PLoS ONE 5(3):
e9594. doi:10.1371/journal.pone.0009594

Editor: Ben L. Kelly, Louisiana State University, United States of
America

Received: November 12, 2009; Accepted: February 15, 2010; Published:
March 9, 2010

Copyright: © 2010 McDonald et al. This is an open-access article
distributed under the terms of the Creative Commons Attribution
License, which permits unrestricted use, distribution, and
reproduction in any medium, provided the original author and source
are credited.

Funding: This work was supported in part by a Program Grant from the
National Health and Medical Research Council (NHMRC) of Australia
(339400) to VNS. DFW is the recipient of an NHMRC R. D. Wright Career
Development Award. The funders had no role in study design, data
collection and analysis, decision to publish, or preparation of the
manuscript.

Competing interests: The authors have declared that no competing
interests exist.

* E-mail: Nathan.Subraman...@qimr.edu.au

http://www.plosone.org/article/info%3Adoi%2F10.1371%2Fjournal.pone.00...

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