Macrophage Migration Inhibitory Factor: A Downregulator of Early T Cell-Dependent IFN-gamma Responses in Plasmodium chabaudi adami (556 KA)-Infected Mice

作者：Malu Diane Tshikudi; Belanger Benoit; Desautels Francois; Kelendji Karine; Dalko Esther; Sanchez Dardon Jaime; Leng Lin; Bucala Richard; Satoskar Abhay R; Scorza Tatiana^*

来源：The Journal of Immunology, 2011, 186(11): 6271-6279.

DOI：10.4049/jimmunol.1003355

Neutralization of macrophage migration inhibitory factor (MIF) increases anti-tumor cytotoxic T cell responses in vivo and IFN-gamma responses in vitro, suggesting a plausible regulatory role for MIF in T cell activation. Considering that IFN-gamma production by CD4(+) T cells is pivotal to resolve murine malaria and that secretion of MIF is induced by Plasmodium chabaudi adami parasites, we investigated the effect of MIF deficiency on the infection with this pathogen. Infections with P. c. adami 556 KA parasites were more efficiently controlled in MIF-neutralized and MIF-deficient (knockout [KO]) BALB/c mice. The reduction in parasitemia was associated with reduced production of IL-4 by non-T/non-B cells throughout patent infection. At day 4 postinfection, higher numbers of activated CD4(+) cells were measured in MIF KO mice, which secreted more IFN-gamma, less IL-4, and less IL-10 than did CD4(+) T cells from wild-type mice. Enhanced IFN-gamma and decreased IL-4 responses also were measured in MIF KO CD4(+) T cells stimulated with or without IL-12 and anti-IL-4 blocking Ab to induce Th1 polarization. However, MIF KO CD4(+) T cells efficiently acquired a Th2 phenotype when stimulated in the presence of IL-4 and anti-IL-12 Ab, indicating normal responsiveness to IL-4/STAT6 signaling. These results suggest that by promoting IL-4 responses in cells other than T/B cells during early P. c. adami infection, MIF decreases IFN-gamma secretion in CD4(+) T cells and, additionally, has the intrinsic ability to render CD4(+) T cells less capable of acquiring a robust Th1 phenotype when stimulated in the presence of IL-12. The Journal of Immunology, 2011, 186: 6271-6279.

• 出版日期2011-6-1