Int J Biol Sci 2011; 7(9):1298-1310. doi:10.7150/ijbs.7.1298

Research Paper

MIF Synergizes with Trypanosoma cruzi Antigens to Promote Efficient Dendritic Cell Maturation and IL-12 Production via p38 MAPK

Cesar A. Terrazas1, EriK Huitron1, Alicia Vazquez1, Imelda Juarez1, Griselda M. Camacho2, Elsa A. Calleja2, Miriam Rodriguez-Sosa1,✉

1. Unidad de Biomedicina, Facultad de Estudios Superiores-Iztacala, Universidad Nacional Autónoma de México (UNAM), C. P. 54090 Estado de México, Mexico.
2. Modulo de Instrumentación, Facultad de Estudios Superiores-Iztacala, Universidad Nacional Autónoma de México (UNAM), C. P. 54090 Estado de México, Mexico.

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Citation:
Terrazas CA, Huitron E, Vazquez A, Juarez I, Camacho GM, Calleja EA, Rodriguez-Sosa M. MIF Synergizes with Trypanosoma cruzi Antigens to Promote Efficient Dendritic Cell Maturation and IL-12 Production via p38 MAPK. Int J Biol Sci 2011; 7(9):1298-1310. doi:10.7150/ijbs.7.1298. Available from http://www.ijbs.com/v07p1298.htm

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Abstract

Macrophage migration inhibitory factor (MIF) has been found to be involved in host resistance to several parasitic infections. To determine the mechanisms of the MIF-dependent responses to Trypanosoma cruzi, we investigated host resistance in MIF-/- mice (on the BALB/c background) during an intraperitoneal infection. We focused on the potential involvement of MIF in dendritic cell (DC) maturation and cytokine production. Following a challenge with 5 x 103 T. cruzi parasites, wild type (WT) mice developed a strong IL-12 response and adequate maturation of the draining mesenteric lymph node DCs and were resistant to infection. In contrast, similarly infected MIF-/- mice mounted a weak IL-12 response, displayed immature DCs in the early phases of infection and rapidly succumbed to T. cruzi infection. The lack of maturation and IL-12 production by the DCs in response to total T. cruzi antigen (TcAg) was confirmed by in vitro studies. These effects were reversed following treatment with recombinant MIF. Interestingly, TcAg-stimulated bone marrow-derived DCs from both WT and MIF-/- mice had increased ERK1/2 MAPK phosphorylation. In contrast, p38 phosphorylation was only upregulated in WT DCs. Reconstitution of MIF to MIF-/- DCs upregulated p38 phosphorylation. The MIF-p38 pathway affected MHC-II and CD86 expression as well as IL-12 production. These findings demonstrate that the MIF-induced early DC maturation and IL-12 production mediates resistance to T. cruzi infection, probably by activating the p38 pathway.

Keywords: Macrophage migration inhibitory factor, Trypanosoma cruzi, macrophages, dendritic cells, p38 MAPK, ERK1/2 MAPK.