title: MIF synergizes with Trypanosoma cruzi antigens to promote efficient dendritic cell maturation and IL-12 production via p38 MAPK.
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 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.
authors: Unidad de Biomedicina, Facultad de Estudios Superiores-Iztacala, Universidad Nacional Autónoma de México-UNAM, C. P. 54090 Estado de México, Mexico.
authors: Cesar A
authors: CA
authors: Terrazas
authors: Erik
authors: E
authors: Huitron
authors: Alicia
authors: A
authors: Vazquez
authors: Imelda
authors: I
authors: Juarez
authors: Griselda M
authors: GM
authors: Camacho
authors: Elsa A
authors: EA
authors: Calleja
authors: Miriam
authors: M
authors: Rodriguez-Sosa
mesh_terms: D000818:Animals; D000953:Antigens, Protozoan / Q000235:genetics / Q000378:metabolism*; D004797:Enzyme-Linked Immunosorbent Assay; D005434:Flow Cytometry; D007371:Interferon-gamma / Q000378:metabolism; D018664:Interleukin-12 / Q000378:metabolism*; D053583:Interleukin-1beta / Q000378:metabolism; D008263:Macrophage Migration-Inhibitory Factors / Q000235:genetics / Q000378:metabolism*; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D018345:Mice, Knockout; D010766:Phosphorylation; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism
chemical_list: D000953:Antigens, Protozoan; D053583:Interleukin-1beta; D008263:Macrophage Migration-Inhibitory Factors; D014409:Tumor Necrosis Factor-alpha; D018664:Interleukin-12; D007371:Interferon-gamma