Journal
MOLECULAR IMMUNOLOGY
Volume 47, Issue 4, Pages 726-737Publisher
PERGAMON-ELSEVIER SCIENCE LTD
DOI: 10.1016/j.molimm.2009.10.037
Keywords
Macrophage migration inhibitory factor; Malaria; Tautomerase activity; Crystal structure; ERK1/2
Categories
Funding
- National Basic Research Program of China [2007CB513100]
- Natural Science Foundation of China [30700761]
Ask authors/readers for more resources
Host-derived macrophage migration inhibitory factor (MIF) has been implicated in the pathogenesis of malaria infection, especially in malarial anemia. Although two Plasmodium parasite-derived MIF orthologs, Plasmodium falciparum MIF and P. berghei MIF were identified recently, the crystal structure and the precise roles of Plasmodium-derived MIFs, particularly in combination with the host MIF, remain unknown. In this study, we identified another MIF ortholog from a rodent-specific P. yoelii (PyMIF). This molecule shares a conserved three-dimensional structure with murine MIF(MmMIF), but with a different substrate binding pattern and much lower tautomerase activity. It could activate host cells via several signaling pathways in vitro, and inhibiting macrophage apoptosis, also similarly to MmMIF. However, we found that PyMIF and MmMIF acted synergistically to activate the MAPK-ERK1/2 signaling pathway at very low concentration but acted antagonistically at higher concentration. Furthermore, we detected PyMIF in the sera of infected mice and found that injection of recombinant PyMIF (rPyMIF) during infection could up-regulate several pro-inflammatory cytokines in vivo and slightly delay the death of infected mice. These data suggest that PyMIF modulates host immune responses together with host MIF and has potential to prolong parasitemia or the chronicity of malaria infection. (C) 2010 Elsevier Ltd. All rights reserved.
Authors
I am an author on this paper
Click your name to claim this paper and add it to your profile.
Reviews
Recommended
No Data Available