Parasite Mif Orthologs

Orthologs of macrophage migration inhibitory factor (MIF) have been identified in dozens of protozoan and nematode parasites, and the properties of many of these have been investigated and reported upon. Crystallographic analyses have revealed close structural similarity of these with human MIF, and many of these parasite MIFs are able to bind directly to the human MIF receptor CD74. Additionally, most parasite MIFs demonstrate tautomerase activity similar to that of the human protein. Parasite MIFs demonstrate many of the pro-inflammatory activities of human MIF, including the ability to regulate macrophage migration, stimulate signal transduction pathways, inhibit apoptosis, and promote production of inflammatory cytokines including IL-8 and TNF-a. These properties indicate that parasite MIFs may be involved in altering the immune response during infection, a role that has been confirmed in a handful of animal model studies. These suggest a mechanism in which parasite MIFs signal to host macrophages to influence the ensuing adaptive immune response in order to promote parasite persistence and transmission. Because of the pathogenic impact of parasite MIFs, therapeutic interventions including small molecule inhibitors and immunizations have been explored. It is hoped that therapies targeting parasite MIFs will provide a novel treatment for an array of chronic, difficult- to-treat infectious diseases.