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Publication : Macrophage migration inhibitory factor (MIF) is critical for the host resistance against Toxoplasma gondii.

First Author  Flores M Year  2008
Journal  FASEB J Volume  22
Issue  10 Pages  3661-71
PubMed ID  18606868 Mgi Jnum  J:140243
Mgi Id  MGI:3813159 Doi  10.1096/fj.08-111666
Citation  Flores M, et al. (2008) Macrophage migration inhibitory factor (MIF) is critical for the host resistance against Toxoplasma gondii. FASEB J 22(10):3661-71
abstractText  Macrophage migration inhibitory factor (MIF) exerts either a protective or a deleterious role in the immune response to different pathogens. We analyzed herein the role of MIF in the host control of toxoplasmosis using MIF(-/-) mice backcrossed to either the BALB/c or the C57BL/6 genetic backgrounds. Both, wild-type (WT) BALB/c and MIF(-/-) BALB/c mice were susceptible to infection with highly virulent RH as well as moderately virulent ME49 strains of T. gondii. MIF(-/-) mice, however, showed greater liver damage and more brain cysts, produced less proinflammatory cytokines, and succumbed significantly faster than WT mice. Bone marrow-derived dendritic cells (BMDCs) from MIF(-/-) mice produced less interleukin-1beta, interleukin-12, and tumor necrosis factor-alpha than WT BMDCs after stimulation with soluble Toxoplasma antigen (STAg). Similar observations were made in CD11c(+) low-density cells isolated from the spleens of MIF(-/-) mice challenged with STAg. MIF(-/-) C57BL/6 mice succumbed to ME49 infection faster than their WT counterparts. C57BL/6 mice that succumbed to infection with the ME49 strain produced less MIF than resistant BALB/c mice similarly infected. Interestingly, an analysis of brains from patients with cerebral toxoplasmosis showed low levels of MIF expression. Together, these findings demonstrate that MIF plays a critical role in mediating host resistance against T. gondii.
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