Int J Biol Sci 2011; 7(9):1298-1310. doi:10.7150/ijbs.7.1298
MIF Synergizes with Trypanosoma cruzi Antigens to Promote Efficient Dendritic Cell Maturation and IL-12 Production via p38 MAPK
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.
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.
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