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Infection and Immunity, June 2006, p. 3170-3179, Vol. 74, No. 6
0019-9567/06/$08.00+0     doi:10.1128/IAI.01648-05
Copyright © 2006, American Society for Microbiology. All Rights Reserved.

Macrophage Migration Inhibitory Factor Contributes to Host Defense against Acute Trypanosoma cruzi Infection

Unidad de Biomedicina, Facultad de Estudios Superiores-Iztacala, Universidad Nacional Autónoma de México (UNAM) Tlalnepantla,¹ Instituto de Investigaciones Biomédicas, UNAM,² Instituto Nacional de Cardiología Ignacio Chávez, Mexico D.F., México,³ Department of Microbiology, The Ohio State University, Columbus, Ohio⁴

Received 7 October 2005/ Returned for modification 12 December 2005/ Accepted 15 March 2006

Macrophage migration inhibitory factor (MIF) is a proinflammatory cytokine that is involved in the host defense against several pathogens. Here we used MIF^–/– mice to determine the role of endogenous MIF in the regulation of the host immune response against Trypanosoma cruzi infection. MIF^–/– mice displayed high levels of blood and tissue parasitemia, developed severe heart and skeletal muscle immunopathology, and succumbed to T. cruzi infection faster than MIF^+/+ mice. The enhanced susceptibility of MIF^–/– mice to T. cruzi was associated with reduced levels of proinflammatory cytokines, such as tumor necrosis factor alpha, interleukin-12 (IL-12), IL-18, gamma interferon (IFN-), and IL-1ß, in their sera and reduced production of IL-12, IFN-, and IL-4 by spleen cells during the early phase of infection. At all time points, antigen-stimulated splenocytes from MIF^+/+ and MIF^–/– mice produced comparable levels of IL-10. MIF^–/– mice also produced significantly less Th1-associated antigen-specific immunoglobulin G2a (IgG2a) throughout the infection, but both groups produced comparable levels of Th2-associated IgG1. Lastly, inflamed hearts from T. cruzi-infected MIF^–/– mice expressed increased transcripts for IFN-, but fewer for IL-12 p35, IL-12 p40, IL-23, and inducible nitric oxide synthase, compared to MIF^+/+ mice. Taken together, our findings show that MIF plays a role in controlling acute T. cruzi infection.

Editor: J. F. Urban, Jr.

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