Toxoplasma gondii: Impaired maturation and pro-inflammatory response of dendritic cells in MIF-deficient mice favors susceptibility to infection

• Published in: Experimental parasitology 2010-11, Vol.126 (3), p.348-358
• Main Authors: Terrazas, Cesar A., Juarez, Imelda, Terrazas, Luis I., Saavedra, Rafael, Calleja, Elsa A., Rodriguez-Sosa, Miriam
• Format: Article
• Language: English
• Subjects: Animals; Antigens, Protozoan - immunology; Brain - parasitology; Cysts; Dendritic cells; Dendritic Cells - immunology; Dendritic Cells - pathology; Disease Progression; Disease Susceptibility - immunology; Histocompatibility Antigens Class II - metabolism; Interleukin-12 - biosynthesis; Intramolecular Oxidoreductases - genetics; Intramolecular Oxidoreductases - physiology; Liver - parasitology; Liver - pathology; Macrophage migration inhibitory factor; Macrophage Migration-Inhibitory Factors - genetics; Macrophage Migration-Inhibitory Factors - physiology; Male; Mice; Mice, Inbred BALB C; Mice, Inbred C57BL; Mice, Knockout; Specific Pathogen-Free Organisms; Toxoplasma - genetics; Toxoplasma - growth & development; Toxoplasma - immunology; Toxoplasma gondii; Toxoplasmosis, Animal - immunology; Up-Regulation
• ISSN: 0014-4894; 1090-2449
• DOI: 10.1016/j.exppara.2010.03.009

Macrophage migration inhibitory factor (MIF) has been found to be involved in host resistance to several parasitic infections. To determine the mechanisms of MIF-dependent responses to Toxoplasma gondii, we investigated host resistance in MIF−/− mice (BALB/c background) during natural oral infection. We focused on the potential involvement of MIF in Dendritic Cell (DC) maturation and IL-12 production. Following oral T. gondii infection, wild type mice developed a strong IL-12 response with an adequate maturation of their draining mesenteric lymph node DC (MLNDC) population and were resistant to challenge with either 40 or 100 cysts (ME49 strain). In contrast, similarly infected MIF−/− mice mounted a weak IL-12 response, displayed immature MLNDCs in the early phases of infection and rapidly succumbed to both type of challenges. Lack of maturation and IL-12 production of DCs in response to T. gondii antigens was confirmed by in vitro studies, and these effects were reversed following treatment with recombinant MIF. These findings demonstrate that MIF-induced early DC maturation and IL-12 production mediate resistance to T. gondii infection.