Macrophage Migration Inhibitory Factor Plays a Critical Role in Mediating Protection against the Helminth ParasiteTaenia crassiceps

Abstract

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-␥), suggesting that the susceptibility of MIF ؊/؊ mice to T. crassiceps was not due to the lack of IFN-␥ production. Interestingly, low levels of both total and specific immunoglobulin G2a were observed in MIF ؊/؊ cysticercotic mice despite the high IFN-␥ 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-␥ 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.

Role for macrophage migration inhibitory factor in asthma

“…These findings suggest that MIF deficiency results in a selective defect in T H 2 priming, or in the B cell response that is necessary for isotype switching. These findings with respect to the humoral response differ from what has been observed during infection with Taenia crassiceps, in which IgE levels are preserved in the absence of MIF (24). These later studies were performed in mice of the same genetic background and T H 2 sensitivity as described here, and the difference in the antibody response may relate to the nature or the duration of the antigenic stimulus by helminthic infection.…”

Macrophage migration inhibitory factor is essential for allergic asthma but not for Th2 differentiation

“…We utilized 6-8-week-old MIF -/-in a BALB/c background obtained as previously described [17,32]. These mice were backcrossed for ten generations onto a BALB/c background.…”

“…A prominent induction of MIF mRNA and protein has been observed in activated Th2 cells, while eosinophils have pre-formed MIF and are able to secrete high quantities of it upon stimulation [28,31]. A role of MIF on Th2 pathologies has been demonstrated by the inefficient control of helminthic infection in the absence of MIF [32,33]. Recent findings suggest that MIF plays an essential role in the physiopathology of experimental pulmonary allergic inflammation and contrary to other studies indicates that MIF is essential for Th2 differentiation [34].…”

Novel Anti-inflammatory Activity of Epoxyazadiradione against Macrophage Migration Inhibitory Factor

“…Higher levels of MIF have been found both systemically and within affected tissues in patients with multiple sclerosis, sepsis, diabetes mellitus, glomerulonephritis, psoriasis, rheumatoid arthritis, systemic lupus erythematosus, atherosclerosis, inflammatory bowel disease, Guillain-Barré syndrome, neuro-Behçet disease, malarial anemia, gastric ulcer, Parkinson disease, hepatocellular carcinoma, breast cancer, and bladder urothelial cell carcinoma (9 -17). MIF also has a role in deter-mining the outcome of infections caused by different parasites, bacteria, and viruses such as helminths (18), Leishmania (19), nematodes (20), malaria (21), Streptococcus (22), and dengue virus (23). Block of endogenous MIF by a small molecule such as (S,R)-3-(4-hydroxyphenyl)-4,5-dihydro-5-isoxazole acetic acid methyl ester (ISO-1) or sulforaphane and neutralization of MIF by anti-MIF antibodies or by plant-derived MIF inhibitors reduces the manifestations of immune inflammatory disorders in numerous preclinical models such as type II collagen-induced arthritis, immunologically induced kidney disease, experimental autoimmune encephalomyelitis, experimental allergic neuritis, immunoinflammatory diabetes, experimental autoimmune myocarditis, irradiation-induced acute pneumonitis, sepsis, and ischemia-reperfusion injury (14, 24 -27).…”