Journal article
Elevated Levels of the Plasmodium yoelii Homologue of Macrophage Migration Inhibitory Factor Attenuate Blood-Stage Malaria
Infection and immunity, v 78(12), pp 5151-5162
Dec 2010
PMID: 20837716
Featured in Collection : UN Sustainable Development Goals @ Drexel
Abstract
The excessive production of proinflammatory cytokines plays a significant role in the pathogenesis of severe malaria. Mammalian macrophage migration inhibitory factor (MIF) (mMIF) is an immune mediator that promotes a sustained proinflammatory response by inhibiting the glucocorticoid-mediated downregulation of inflammation. In addition,
Plasmodium
parasites also encode a homologue of mammalian MIF that is expressed in asexual-stage parasites. We used the
Plasmodium yoelii
murine model to study the potential role of parasite-encoded MIF in the pathogenesis of malaria. Antibodies raised against purified, non-epitope-tagged
P. yoelii
MIF (
Py
MIF) were used to localize expression in trophozoite- and schizont-stage parasites and demonstrate extracellular release.
In vitro
, recombinant
Py
MIF was shown to actively induce the chemotaxis of macrophages but did not induce or enhance tumor necrosis factor alpha (TNF-α) production from peritoneal macrophages. To examine the role of parasite-derived
Py
MIF
in vivo
, two transgenic parasite lines that constitutively overexpress
Py
MIF were generated, one in a nonlethal
P. yoelii
17X background [
Py
17X-MIF(+)] and the other in a lethal
P. yoelii
17XL background [
Py
17XL-MIF(+)]. Challenge studies with transgenic parasites in mice showed that the increased expression of
Py
MIF resulted in a reduction in disease severity. Mice infected with
Py
17X-MIF(+) developed lower peak parasitemia levels than controls, while malaria-associated anemia was unaltered. Infection with
Py
17XL-MIF(+) resulted in a prolonged course of infection and a reduction in the overall mortality rate. Combined, the data indicate that parasite-derived MIF does not contribute significantly to immunopathology but, through its chemotactic ability toward macrophages, may attenuate disease and prolong infection of highly virulent parasite isolates.
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Details
- Title
- Elevated Levels of the Plasmodium yoelii Homologue of Macrophage Migration Inhibitory Factor Attenuate Blood-Stage Malaria
- Creators
- Swati Thorat - Center for Molecular Parasitology, Department of Microbiology and Immunology, Drexel University College of Medicine, Philadelphia, Pennsylvania 19129Thomas M Daly - Center for Molecular Parasitology, Department of Microbiology and Immunology, Drexel University College of Medicine, Philadelphia, Pennsylvania 19129Lawrence W Bergman - Center for Molecular Parasitology, Department of Microbiology and Immunology, Drexel University College of Medicine, Philadelphia, Pennsylvania 19129James M Burns - Center for Molecular Parasitology, Department of Microbiology and Immunology, Drexel University College of Medicine, Philadelphia, Pennsylvania 19129
- Publication Details
- Infection and immunity, v 78(12), pp 5151-5162
- Publisher
- American Society for Microbiology (ASM)
- Resource Type
- Journal article
- Language
- English
- Academic Unit
- Microbiology and Immunology; [Retired Faculty]
- Web of Science ID
- WOS:000284213600018
- Scopus ID
- 2-s2.0-78649971658
- Other Identifier
- 991014877924704721
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InCites Highlights
Data related to this publication, from InCites Benchmarking & Analytics tool:
- Web of Science research areas
- Immunology
- Infectious Diseases