| The major etiological agents of lymphatic filariasis Wuchereria bancrofti and Brugia malayi infect over 128 million people worldwide. A dominant immunological phenotype of infection is a loss of T cell proliferation and an immune response that is dominated by Th2-type cytokines. Although the specific roles for Th1 and Th2 responses in human pathology and immunity remain unresolved, parasite development within a Th2-dominant environment appears to convey an advantage for long-term parasite survival. It is possible that filariae play an active role in modifying host immunity in a way that promotes chronicity. Bm-MIF-1, a parasite-derived homologue of the human cytokine, macrophage migration inhibitory factor (MIF), has been implicated as an immune modifier. We assessed the potential of DNA or protein immunizations to generate protection using the BALB/c B. malayi model. Immunization with a Bm-mif-1 DNA vaccine induced a modest antibody response and a 40% reduction in larval load 7 days after L3 challenge. In contrast, the Bm-MIF-1 protein immunizations, which induced high levels of anti-Bm-MIF IgG1, resulted in a 40% increase in larval survival at day 13 post-challenge. These results suggest that the parasite-derived and host-derived MIF proteins play opposing roles in the regulation of larval survival in the mouse model. To further explore a role for parasite-derived MIF as an immune modulator, we stimulated human monocyte-derived dendritic cells and monocytes with recombinant Bm-MIF-1. Cytokine expression from Bm-MIF-1 stimulated dendritic cells was biased towards IL-10, a Th2 cytokine. A similar effect was not seen with monocytes. Finally, we characterized three mif genes in the non-parasitic, free-living nematode C. elegans. RT-PCR, gfp expression and antibody staining suggest similar expression patterns for the mif genes in both the parasitic and non-parasitic nematodes. An upregulation of Ce-mif expression during the dauer stage of development suggests that MIF is involved in homeostatic mechanisms not only in mammals, but in invertebrates as well. |
