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-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.
Flores
Marcos
M
Unidad de Biomedicina, FES-Iztacala, UNAM. Av. de los Barrios #1, Los Reyes Iztacala, 54090 Tlalnepantla, Mexico City, Mexico.
Saavedra
Rafael
R
Bautista
Rocio
R
Viedma
Rubi
R
Tenorio
Eda P
EP
Leng
Lin
L
Sánchez
Yuriko
Y
Juárez
Imelda
I
Satoskar
Anjali A
AA
Shenoy
Asha S
AS
Terrazas
Luis I
LI
Bucala
Richard
R
Barbi
Joseph
J
Satoskar
Abhay R
AR
Rodriguez-Sosa
Miriam
M
D000818:Animals; D001921:Brain / Q000378:metabolism / Q000469:parasitology; D016207:Cytokines / Q000096:biosynthesis; D003713:Dendritic Cells / Q000276:immunology; D004660:Encephalitis / Q000276:immunology / Q000469:parasitology / Q000473:pathology; D020022:Genetic Predisposition to Disease; D006505:Hepatitis / Q000276:immunology / Q000469:parasitology / Q000473:pathology; D006790:Host-Parasite Interactions / Q000235:genetics / Q000276:immunology; D006801:Humans; D007113:Immunity, Innate / Q000235:genetics; D019746:Intramolecular Oxidoreductases / Q000235:genetics / Q000502:physiology*; D008263:Macrophage Migration-Inhibitory Factors / Q000235:genetics / Q000502:physiology*; D051379:Mice; D008817:Mice, Mutant Strains; D017942:Nitric Acid / Q000378:metabolism; D051195:Toll-Like Receptor 2 / Q000096:biosynthesis; D014122:Toxoplasma / Q000472:pathogenicity; D014123:Toxoplasmosis / Q000235:genetics* / Q000276:immunology / Q000473:pathology; D016781:Toxoplasmosis, Cerebral / Q000276:immunology / Q000469:parasitology / Q000473:pathology; D014774:Virulence
D016207:Cytokines; D008263:Macrophage Migration-Inhibitory Factors; C493486:Tlr2 protein, mouse; D051195:Toll-Like Receptor 2; D017942:Nitric Acid; D019746:Intramolecular Oxidoreductases; C076231:Mif protein, mouse