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

被引:24
|
作者
Terrazas, Cesar A. [1 ]
Huitron, Erik [1 ]
Vazquez, Alicia [1 ]
Juarez, Imelda [1 ]
Camacho, Griselda M.
Calleja, Elsa A.
Rodriguez-Sosa, Miriam [1 ]
机构
[1] Univ Nacl Autonoma Mexico, Fac Estudios Super Iztacala, Unidad Biomed, Mexico City 54090, Estado De Mexic, Mexico
来源
INTERNATIONAL JOURNAL OF BIOLOGICAL SCIENCES | 2011年 / 7卷 / 09期
关键词
Macrophage migration inhibitory factor; Trypanosoma cruzi; macrophages; dendritic cells; p38; MAPK; ERK1/2; MIGRATION-INHIBITORY FACTOR; ACTIVATED PROTEIN-KINASE; TOLL-LIKE RECEPTOR-2; SIGNAL-REGULATED KINASE; IN-VIVO; GLYCOSYLPHOSPHATIDYLINOSITOL ANCHORS; CHAGAS-DISEASE; NITRIC-OXIDE; IMMUNE-RESPONSES; CUTTING EDGE;
D O I
10.7150/ijbs.7.1298
中图分类号
Q5 [生物化学]; Q7 [分子生物学];
学科分类号
071010 ; 081704 ;
摘要
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 10(3) 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.
引用
收藏
页码:1298 / 1310
页数:13
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