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

作者：Flores Marcos; Saavedra Rafael; Bautista Rocio; Viedma Rubi; Tenorio Eda P; Leng Lin; Sanchez Yuriko; Juarez Imelda; Satoskar Anjali A; Shenoy Asha S; Terrazas Luis I; Bucala Richard; Barbi Joseph; Satoskar Abhay R; Rodriguez Sosa Miriam^*

来源：The FASEB Journal, 2008, 22(10): 3661-3671.

DOI：10.1096/fj.08-111666

• proinflammatory cytokines
• innate immunity
• cerebral toxoplasmosis

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-1 beta, interleukin-12, and tumor necrosis factor-alpha than WT BMDCs after stimulation with soluble Toxoplasma antigen (STAB). Similar observations were made in CD11c(+) low-density cells isolated from the spleens of MIF-/- mice challenged with STAB. 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.

• 出版日期2008-10