Macrophage migration inhibitory factor plays a critical role in mediating protection against the helminth parasite Taenia crassiceps.
To determine the role of endogenous migration inhibitory factor (MIF) in regulation of immune response during murine cysticercosis caused by the helminth parasite Taenia crassiceps, we analyzed the course of T. crassiceps infection in MIF(-/-) BALB/c mice. MIF(-/-) mice were highly susceptible to T. crassiceps and developed significantly higher parasite loads compared to similarly infected MIF(+/+) mice. Throughout the course of infection, Taenia crassiceps soluble antigen-stimulated spleen cells from both MIF(+/+) and MIF(-/-) mice produced significant and comparable levels of interleukin-4 (IL-4), but those from MIF(-/-) mice produced significantly more IL-13, as well as gamma interferon (IFN-gamma), suggesting that the susceptibility of MIF(-/-) mice to T. crassiceps was not due to the lack of IFN-gamma production. Interestingly, low levels of both total and specific immunoglobulin G2a were observed in MIF(-/-) cysticercotic mice despite the high IFN-gamma levels; in addition, peritoneal macrophages obtained from T. crassiceps-infected MIF(-/-) mice at different time points failed to respond efficiently to stimulation in vitro with lipopolysaccharide plus IFN-gamma and produced significantly lower levels of IL-12, tumor necrosis factor alpha, and NO compared to those from MIF(+/+) mice. These findings demonstrate that MIF plays a critical role in mediating protection against T. crassiceps in vivo. Moreover, these findings also suggest that impaired macrophage function rather than the lack of Th1 development may be responsible for mediating susceptibility to T. crassiceps.
Rodríguez-Sosa
Miriam
M
Department of Immunology, Instituto Nacional de Cardiología Ignacio Chávez, Mexico, D.F. 14080 Mexico.
Rosas
Lucia E
LE
David
John R
JR
Bojalil
Rafael
R
Satoskar
Abhay R
AR
Terrazas
Luis I
LI
D000818:Animals; D000909:Antibodies, Helminth / Q000097:blood; D003551:Cysticercosis / Q000276:immunology*; D005260:Female; D007073:Immunoglobulin E / Q000097:blood; D007074:Immunoglobulin G / Q000097:blood / Q000145:classification; D007371:Interferon-gamma / Q000494:pharmacology; D008263:Macrophage Migration-Inhibitory Factors / Q000502:physiology*; D051379:Mice; D008807:Mice, Inbred BALB C; D009569:Nitric Oxide / Q000096:biosynthesis; D018417:Th1 Cells / Q000276:immunology; D018418:Th2 Cells / Q000276:immunology
D000909:Antibodies, Helminth; D007074:Immunoglobulin G; D008263:Macrophage Migration-Inhibitory Factors; D009569:Nitric Oxide; D007073:Immunoglobulin E; D007371:Interferon-gamma