Structural and functional comparison of MIF ortholog from Plasmodium yoelii with MIF from its rodent host

Autor: Xiao-Dong Su, Zhifu Han, Yanfeng Zhou, Lianhui Zhang, Dingding Shao, Lingyi Bu, Xiang Zhong, Zhensheng Wang, Heng Wang, Yahui Lin
Rok vydání: 2010
Předmět:
Cell Survival
MAP Kinase Signaling System
medicine.medical_treatment
Molecular Sequence Data
Immunology
Apoptosis
chemical and pharmacologic phenomena
Parasitemia
Crystallography
X-Ray
Protein Structure
Secondary
Cell Line
Host-Parasite Interactions
Microbiology
Mice
Immune system
Proto-Oncogene Proteins
parasitic diseases
otorhinolaryngologic diseases
medicine
Animals
Amino Acid Sequence
Macrophage Migration-Inhibitory Factors
Molecular Biology
biology
Macrophages
Plasmodium falciparum
Plasmodium yoelii
Macrophage Activation
biology.organism_classification
medicine.disease
Recombinant Proteins
In vitro
Malaria
Up-Regulation
Enzyme Activation
Cytokine
Proto-Oncogene Proteins c-bcl-2
Structural Homology
Protein
Injections
Intravenous
Macrophage migration inhibitory factor
Inflammation Mediators
Signal transduction
Signal Transduction
Zdroj: Molecular Immunology. 47:726-737
ISSN: 0161-5890
DOI: 10.1016/j.molimm.2009.10.037
Popis: 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.
Databáze: OpenAIRE
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