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

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-1β, interleukin-12, and tumor necrosis factor-α 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 ...