Title
MIF contributes to **Trypanosoma brucei** associated immunopathogenicity development MIF contributes to **Trypanosoma brucei** associated immunopathogenicity development
Author
Faculty/Department
Faculty of Pharmaceutical, Biomedical and Veterinary Sciences. Pharmacy
Publication type
article
Publication
San Francisco, Calif. ,
Subject
Biology
Human medicine
Source (journal)
PLoS pathogens. - San Francisco, Calif.
Volume/pages
10(2014) :9 , 13 p.
ISSN
1553-7366
1553-7366
Article Reference
e1004414
Carrier
E-only publicatie
Target language
English (eng)
Full text (Publishers DOI)
Abstract
African trypanosomiasis is a chronic debilitating disease affecting the health and economic well-being of many people in developing countries. The pathogenicity associated with this disease involves a persistent inflammatory response, whereby M1-type myeloid cells, including Ly6C(high) inflammatory monocytes, are centrally implicated. A comparative gene analysis between trypanosusceptible and trypanotolerant animals identified MIF (macrophage migrating inhibitory factor) as an important pathogenic candidate molecule. Using MIF-deficient mice and anti-MIF antibody treated mice, we show that MIF mediates the pathogenic inflammatory immune response and increases the recruitment of inflammatory monocytes and neutrophils to contribute to liver injury in Trypanosoma brucei infected mice. Moreover, neutrophil-derived MIF contributed more significantly than monocyte-derived MIF to increased pathogenic liver TNF production and liver injury during trypanosome infection. MIF deficient animals also featured limited anemia, coinciding with increased iron bio-availability, improved erythropoiesis and reduced RBC clearance during the chronic phase of infection. Our data suggest that MIF promotes the most prominent pathological features of experimental trypanosome infections (i.e. anemia and liver injury), and prompt considering MIF as a novel target for treatment of trypanosomiasis-associated immunopathogenicity.
E-info
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Full text (open access)
https://repository.uantwerpen.be/docman/irua/c5286a/130112.pdf