Title: Distinct immunoregulatory properties of macrophage migration inhibitory factors encoded by Eimeria parasites and their chicken host Authors
|Kim, Duk Kyung|
|Bosch, Marc Pages|
Submitted to: Vaccine
Publication Type: Peer Reviewed Journal
Publication Acceptance Date: May 11, 2012
Publication Date: June 5, 2012
Citation: Jang, S.I., Lillehoj, H.S., Lee, S.H., Kim, D., Bosch, M., Hong, Y.H., Min, W., Lillehoj, E.P. 2012. Distinct immunoregulatory properties of macrophage migration inhibitory factors encoded by Eimeria parasites and their chicken host. Vaccine. 29:8998-9004. Interpretive Summary: Avian diseases such as coccidiosis and Clostridium infections, which are caused by local infection of gut by intestinal protozoan parasites and bacteria, respectively, elicit acute local inflammatory responses. Understanding basic immunological mechanisms of host-pathogen interaction is critical to develop logical disease control strategies. In this paper, ARS scientists describe the important role of a soluble factor which is secreted by activated macrophages after infection with coccidiosis. They show that macrophage migration inhibitory factor (MIF), promotes the production of cytokines which are involved in host defense against a variety of microorganisms including protozoan parasites. Furthermore, molecular analysis of genes which encode host-derived and pathogen-derived MIF molecules demonstrated biochemical and functional differences among these MIF molecules. The results also show that the induction of protective immunity using recombinant parasite-derived MIF in young birds provide the first scientific evidence that MIF can be a potential vaccine antigen against avian coccidiosis for the first time. These results provide important new information that will facilitate the development of non-living vaccines against coccidiosis in poultry.
Technical Abstract: Macrophage migration inhibitory factor (MIF) is a proinflammatory cytokine that plays an important role in host defense against a variety of microorganisms including protozoan parasites. Interestingly, some microbial pathogens also express a MIF-like protein, although its role in disease pathogenesis is not well understood. The aim of this study was to compare an Eimeria-encoded MIF (E.MIF) protein with chicken MIF (C.MIF) on the basis of their structural, immunological, and biological properties. E.MIF and C.MIF proteins, each with a glutathione S-transferase epitope tag, were expressed in E. coli or COS-7 cells and purified by glutathione affinity chromatography. Rabbit antisera against the purified proteins demonstrated their mutual immunological cross-reactivity on Western blots, and immunolocalized intracellular native E.MIF to the Eimeria schizont, merozoite, and oocyst life cycle stages. HD11 chicken macrophages treated in vitro with C.MIF recombinant protein expressed increased levels of transcripts encoding interleukin-6 (IL-6), IL-17, and tumor necrosis factor superfamily member 17 (TNFSF17), but decreased levels of IL-8 transcripts, compared with cells treated with the PBS control; similar treatment with E.MIF only down-regulated IL-8 transcripts. Unlike recombinant E.MIF, C.MIF exhibited in vitro chemotactic activity for HD11 cells. Conversely, E.MIF, but not C.MIF, enhanced protection against experimental Eimeria infection, compared with the PBS control. These studies provide evidence for overlapping structural and antigenic properties, but distinct immunoregulatory roles, of E.MIF and C.MIF.