Macrophage migration inhibitory factor contributes to host defense against acute Trypanosoma cruzi infection.
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-gamma), and IL-1beta, in their sera and reduced production of IL-12, IFN-gamma, 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-gamma, 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.
Reyes
José L
JL
Unidad de Biomedicina, FES-Iztacala, UNAM, Av. De los Barrios #1, Los Reyes Iztacala, 54090 Tlalnepantla, Edo. de México, Mexico.
Terrazas
Luis I
LI
Espinoza
Bertha
B
Cruz-Robles
David
D
Soto
Virgilia
V
Rivera-Montoya
Irma
I
Gómez-García
Lorena
L
Snider
Heidi
H
Satoskar
Abhay R
AR
Rodríguez-Sosa
Miriam
M
D000208:Acute Disease; D000818:Animals; D000913:Antibodies, Protozoan / Q000097:blood; D014355:Chagas Disease / Q000276:immunology* / Q000473:pathology; D007074:Immunoglobulin G / Q000097:blood; D007371:Interferon-gamma / Q000096:biosynthesis; D007375:Interleukin-1 / Q000096:biosynthesis; D018664:Interleukin-12 / Q000096:biosynthesis; D008263:Macrophage Migration-Inhibitory Factors / Q000502:physiology*; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D018482:Muscle, Skeletal / Q000473:pathology; D009206:Myocardium / Q000473:pathology; D052247:Nitric Oxide Synthase Type II / Q000235:genetics; D018512:Parasitemia / Q000276:immunology; D012333:RNA, Messenger / Q000032:analysis; D014349:Trypanosoma cruzi / Q000276:immunology; D014409:Tumor Necrosis Factor-alpha / Q000096:biosynthesis
D000913:Antibodies, Protozoan; D007074:Immunoglobulin G; D007375:Interleukin-1; D008263:Macrophage Migration-Inhibitory Factors; D012333:RNA, Messenger; D014409:Tumor Necrosis Factor-alpha; D018664:Interleukin-12; D007371:Interferon-gamma; D052247:Nitric Oxide Synthase Type II