Macrophage migration inhibitory factor (MIF) of the protozoan parasite Eimeria influences the components of the immune system of its host, the chicken

Abstract

Macrophage migration inhibitory factor (MIF) is a soluble factor produced by sensitized T lymphocytes that inhibits the random migration of macrophages. Homologues of MIF from invertebrates have been identified, making it an interesting molecule from a functional perspective. In the present study, the localization of a parasite MIF protein as well as its effect on the host was characterized. Western blot analysis shows that Eimeria MIF (EMIF) is found during all parasite developmental stages tested. Transmission electron microscopy shows that MIF is distributed throughout cytosol and nucleus of Eimeria acervulina merozoites. Immunohistochemical analysis suggests that EMIF may be released into the surrounding tissues as early as 24h after infection, while later during oocyst formation, MIF expression is localized to areas immediately surrounding the oocysts, as well as in wall-forming bodies. The chemotaxis assay revealed an inhibitory function of EMIF on chicken monocyte migration. Quantitative real-time PCR was performed to examine the effect of EMIF on host immune system by measuring the transcripts of inflammatory mediators. An ex vivo stimulation study showed that E. acervulina MIF (EaMIF) enhanced expression of pro-inflammatory cytokines and chemokines in the presence of lipopolysaccharide (LPS). Furthermore, sequential treatment of adherent peripheral blood mononuclear cells with EaMIF, chicken MIF, and LPS in 2-h intervals led to the highest levels of interleukin (IL)-1B, chemokine CCLi3, IL-18, and interferon-gamma mRNA expression. This study shows that parasite MIF is widely expressed and may have potential effects on the immune system of the host.